Gene Detail

Gene Symbol ALK
Synonyms CD246 | NBLST3
Gene Description ALK, anaplastic lymphoma kinase, is a receptor in the insulin receptor superfamily and is a key regulator of neuronal development (PMID: 21502284) and also promotes cell proliferation through activation of MAPK and PI3K signaling pathways (PMID: 27573755). Alk activating mutations, rearrangements, and fusions have been identified in various cancers (PMID: 22649787), including EML4-ALK in non-small cell lung cancer (PMID: 30108712, PMID: 30194140), and a number of mutations confer resistance in the context of Alk fusions (PMID: PMID: 25749034, PMID: 21948233).
Entrez Id 238
Chromosome 2
Map Location 2p23.2-p23.1
Canonical Transcript NM_004304

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
E1303K missense unknown ALK E1303K lies within the protein kinase domain of the Alk protein (UniProt.org). E1303K has been identified in the scientific literature (PMID: 29978950), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
G1137R missense no effect - predicted ALK G1137R lies within the protein kinase domain of the Alk protein (UniProt.org). G1137R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
D1249fs frameshift loss of function - predicted ALK D1249fs results in a change in the amino acid sequence of the Alk protein beginning at aa 1249 of 1620, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the ATP binding site, D1249fs is predicted to lead to a loss of Alk protein function (UniProt.org).
V163L missense unknown ALK V163L lies within the extracellular domain of the Alk protein (UniProt.org). V163L has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
F1174I missense gain of function ALK F1174I lies within the protein kinase domain of the Alk protein (UniProt.org). F1174I results in ligand-independent phosphorylation of the Alk protein, activation of Erk, Stat3 pathways, and is transforming in cell culture (PMID: 23104988).
R1113Q missense unknown ALK R1113Q lies within the cytoplasmic domain of the Alk protein (UniProt.org). R1113Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
F1174C missense gain of function ALK F1174C lies within the protein kinase domain of the Alk protein (UniProt.org). F1174C confers a gain of function to Alk, as indicated by constitutive Alk phosphorylation in cell culture (PMID: 24509625, PMID: 22072639).
D1203N missense unknown ALK D1203N lies within the protein kinase domain of the Alk protein (UniProt.org). D1203N has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK and ALK L1196M (PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
E994K missense no effect - predicted ALK E994K does not lie within any known functional domains of the Alk protein (UniProt.org). E994K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
A1266V missense no effect - predicted ALK A1266V lies within the protein kinase domain of the Alk protein (UniProt.org). A1266V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
G1269A missense unknown ALK G1269A lies within the protein kinase domain of the Alk protein (UniProt.org). G1269A has been demonstrated to occur as a secondary resistance mutation in the context of ALK rearrangement (PMID: 23344087, PMID: 22235099, PMID: 29872693), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
K1062M missense gain of function ALK K1062M lies within the protein kinase domain of the Alk protein (UniProt.org). K1062M confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k-Akt and Mapk pathway activation (PMID: 21596819).
L1122V missense unknown ALK L1122V lies within the protein kinase domain of the Alk protein (UniProt.org). L1122V has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
I1461V missense unknown ALK I1461V lies within the cytoplasmic domain of the Alk protein (UniProt.org). I1461V has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
R401Q missense no effect - predicted ALK R401Q lies within the MAM domain 1 of the Alk protein (UniProt.org). R401Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted have no effect on Alk protein function.
amp none no effect ALK amplification indicates an increased number of copies of the ALK gene. However, the mechanism causing the increase is unspecified.
A195V missense no effect - predicted ALK A195V lies within the extracellular domain of the Alk protein (UniProt.org). A195V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
D1091N missense unknown ALK D1091N lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1091N was observed to increase ERK activation in the presence of agonist antibodies (PMID: 23104988) and has demonstrated sensitivity to ALK inhibitors (PMID: 26786851, PMID: 28455243), but is unable to transform cultured cells (PMID: 23104988).
V1545I missense no effect - predicted ALK V1545I does not lie within any known functional domains of the Alk protein (UniProt.org). V1545I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
A585T missense no effect - predicted ALK A585T lies within the MAM domain 2 of the Alk protein (UniProt.org). A585T has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
A1200V missense no effect - predicted ALK A1200V lies within the protein kinase domain of the Alk protein (UniProt.org). A1200V demonstrates kinase activity comparable to wild-type Alk in culture (PMID: 25517749) and therefore, is predicted to have no effect on Alk protein function.
G1202del deletion unknown ALK G1202del results in the deletion of an amino acid in the protein kinase domain of the Alk protein at amino acid 1202 (UniProt.org). G1202del has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
L1152P missense unknown ALK L1152P lies within the protein kinase domain of the Alk protein (UniProt.org). L1152P has been demonstrated to confer drug resistance in in the context of ALK rearrangement in culture (PMID: 24675041), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
F1245L missense unknown ALK F1245L lies within the protein kinase domain of the Alk protein (UniProt.org). F1245L has been identified in sequencing studies (PMID: 18923524), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
G689V missense unknown ALK G689V does not lie within any known functional domains of the Alk protein (UniProt.org). G689V has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
L1152R missense unknown ALK L1152R lies within the protein kinase domain of the Alk protein (UniProt.org). L1152R has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 21791641, PMID: 27091190), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, May 2018). Y
C990R missense unknown ALK C990R lies within the protein kinase domain of the Alk protein (UniProt.org). C990R has not been biochemically characterized, but in one of two cell lines, C990R increased cell proliferation and cell viability above wild-type Alk (PMID: 29533785).
V1180L missense unknown ALK V1180L lies within the protein kinase domain of the Alk protein (UniProt.org). V1180L has been demonstrated to occur as a secondary resistance mutation in the context of EML4-ALK (PMID: 25228534, PMID: 27432227), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018). Y
I1179V missense unknown ALK I1179V lies within the protein kinase domain of the Alk protein (UniProt.org). I1179V has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
I1171S missense unknown ALK I1171S lies within the protein kinase domain of the Alk protein (UniProt.org). I1171S has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859, PMID: 25393796), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
P336S missense no effect - predicted ALK P336S lies within the MAM domain 1 of the Alk protein (UniProt.org). P336S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
P1139S missense unknown ALK P1139S lies within the protein kinase domain of the Alk protein (UniProt.org). P1139S has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
L1198P missense gain of function - predicted ALK L1198P lies within the protein kinase domain of the Alk protein (UniProt.org). L1198P is predicted to confer a gain of function on the Alk protein as indicated by increased phosphorylation of Alk and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK in culture (PMID: 21948233). Y
rearrange unknown unknown ALK rearrangement indicates an unspecified rearrangement of the ALK gene.
V66A missense unknown ALK V66A lies within the extracellular domain of the Alk protein (UniProt.org). V66A has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2018).
S1206Y missense unknown ALK S1206Y lies within the protein kinase domain of the Alk protein (UniProt.org). S1206Y has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK rearrangements (PMID: 22277784, PMID: 24675041, PMID: 25727400), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018). Y
R1212H missense unknown ALK R1212H lies within the protein kinase domain of the Alk protein (UniProt.org). R1212H has been identified in sequencing studies (PMID: 21499247, PMID: 28912153), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
R1192P missense gain of function ALK R1192P lies within the protein kinase domain of the Alk protein (UniProt.org). R1192P confers a gain of function to the Alk protein as demonstrated by transformed cells and increased downstream signalling, although less robustly than other activating mutants (PMID: 21838707).
G1123S missense unknown ALK G1123S lies within the protein kinase domain of the Alk protein (UniProt.org). G1123S has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK rearrangement (PMID: 26134233, PMID: 21948233), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
P1298S missense unknown ALK P1298S lies within the protein kinase domain of the Alk protein (UniProt.org). P1298S has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
R1209Q missense loss of function - predicted ALK R1209Q lies within the protein kinase domain of the Alk protein (UniProt.org). R1209Q has not been biochemically characterized, but in one of two cell lines, R1209Q had decreased cell proliferation and cell viability as compared to wild-type Alk (PMID: 29533785) and therefore, is predicted to result in a loss of Alk protein function.
I1171T missense gain of function ALK I1171T lies within the protein kinase domain of the Alk protein (UniProt.org). I1171T confers a gain of function on the Alk protein as indicated by ligand-independent autophosphorylation, activation of Erk1/2, and cell transformation (PMID: 29907598), and has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859). Y
R1275Q missense gain of function ALK R1275Q lies within the protein kinase domain of the Alk protein (UniProt.org). R1275Q confers a gain of function to the Alk protein as demonstrated by transformation activity in cell culture and increased downstream signalling in in vitro assays (PMID: 21838707, PMID: 29533785).
R1275L missense unknown ALK R1275L is a hotspot mutation, lies within the protein kinase domain of the Alk protein (UniProt.org, PMID: 18923525, PMID: 21242967). R1275L has been identified in sequencing studies (PMID: 25517749, PMID: 27888620), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
C1156F missense unknown ALK C1156F lies within the protein kinase domain of the Alk protein (UniProt.org). C1156F has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25749034), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
G1552R missense no effect - predicted ALK G1552R does not lie within any known functional domains of the Alk protein (UniProt.org). G1552R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
G875R missense no effect - predicted ALK G875R does not lie within any known functional domains of the Alk protein (UniProt.org). G875R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
Y1278S missense gain of function ALK Y1278S is a hotspot mutation that lies within the activation loop of the Alk protein (PMID: 24060861, PMID: 25071110). Y1278S results in constitutive activation of Alk and is transforming in cell culture (PMID: 25517749, PMID: 29084134).
G922R missense unknown ALK G922R does not lie within any known functional domains of the Alk protein (UniProt.org). G922R has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
F457L missense no effect - predicted ALK F457L lies within the LDL-receptor class A domain of the Alk protein (UniProt.org). F457L has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
P1599S missense unknown ALK P1599S lies within the cytoplasmic domain of the Alk protein (UniProt.org). P1599S has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
P858S missense no effect - predicted ALK P858S does not lie within any known functional domains of the Alk protein (UniProt.org). P858S has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and is predicted to have no effect on Alk protein function.
F1245Q missense unknown ALK F1245Q lies within the protein kinase domain of the Alk protein (UniProt.org). F1245Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
H1030P missense unknown ALK H1030P lies within the extracellular domain of the ALK protein (UniProt.org). H1030P has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
N1178H missense unknown ALK N1178H lies within the protein kinase domain of the Alk protein (UniProt.org). N1178H has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25749034), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
L560F missense no effect - predicted ALK L560F lies within the MAM domain 2 of the Alk protein (UniProt.org). L560F has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
D1529G missense unknown ALK D1529G lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1529G has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
I1171N missense gain of function ALK I1171N lies within the protein kinase domain of the Alk protein (UniProt.org). I1171N results in increased ligand-independent Alk phosphorylation, activation of the Stat pathway, and is transforming in cell culture (PMID: 23239810, PMID: 21838707), and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 27565911). Y
R311H missense unknown ALK R311H lies within the MAM domain 1 of the Alk protein (UniProt.org). R311H has been identified in the scientific literature (PMID: 23202128, PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
P36S missense unknown ALK P36S lies within the extracellular domain of the Alk protein (UniProt.org). P36S has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
R133H missense no effect - predicted ALK R133H lies within the extracellular domain of the Alk protein (UniProt.org). R133H has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
S1206F missense unknown ALK S1206F lies within the protein kinase domain of the Alk protein (UniProt.org). S1206F has been identified in the scientific literature (PMID: 27565908), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
L1196M missense gain of function - predicted ALK L1196M lies within the protein kinase domain of the Alk protein (UniProt.org). L1196M is predicted to confer a gain of function to the Alk protein as demonstrated by transformation activity and modest autophosphorylation of Alk in culture (PMID: 25517749), and confers resistance to Alk inhibitors in the context of ALK rearrangements in culture (PMID: 21613408, PMID: 25421750). Y
E717K missense unknown ALK E717K lies within the extracellular domain of the Alk protein (UniProt.org). E717K has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
R753Q missense unknown ALK R753Q lies within the extracellular domain of the Alk protein (UniProt.org). R753Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
K894T missense unknown ALK K894T lies within the extracellular domain of the Alk protein (UniProt.org). K894T has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
W501* nonsense loss of function - predicted ALK W501* results in a premature truncation of the Alk protein at amino acid 501 of 1620 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W501* is predicted to lead to a loss of Alk protein function.
E1210K missense unknown ALK E1210K lies within the protein kinase domain of the Alk protein (UniProt.org). E1210K has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK and EML4-ALK (PMID: 25749034, PMID: 25914136), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
wild-type none no effect Wild-type ALK indicates that no mutation has been detected within the ALK gene.
positive unknown unknown ALK positive indicates the presence of the ALK gene, mRNA, and/or protein.
G1128A missense gain of function ALK G1128A lies within the protein kinase domain of the Alk protein (UniProt.org). G1128A confers a gain of function to the Alk protein as demonstrated by increased downstream signaling in vitro and transformation in cultured cells (PMID: 21838707).
M1166R missense gain of function ALK M1166R lies within the protein kinase domain of the Alk protein (UniProt.org). M1166R confers a gain of function to the Alk protein, as indicated by ligand-independent activation of the Alk protein and increased Erk and Stat3 phosphorylation in cell culture (PMID: 23104988).
L1256F missense unknown ALK L1256F lies within the protein kinase domain of the Alk protein (UniProt.org). L1256F has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
S711R missense no effect - predicted ALK S711R does not lie within any known functional domains of the Alk protein (UniProt.org). S711R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
L1198H missense unknown ALK L1198H lies within the protein kinase domain of the Alk protein (UniProt.org). L1198H has not been biochemically characterized, however, has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534). Y
G1201E missense gain of function ALK G1201E lies within the protein kinase domain of the Alk protein (UniProt.org). G1201E confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation in culture (PMID: 21596819).
A1047T missense unknown ALK A1047T lies within the transmembrane domain of the Alk protein (UniProt.org). A1047T has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Nov 2018).
L868Q missense unknown ALK L868Q lies within the extracellular domain of the Alk protein (UniProt.org). L868Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
F1174L missense gain of function ALK F1174L lies within the protein kinase domain of the Alk protein (UniProt.org). F1174L confers a gain of function to the Alk protein as indicated by transformation activity and increased cell proliferation in culture (PMID: 18923525, PMID: 29533785, PMID: 29907598), and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 21030459). Y
V476A missense no effect - predicted ALK V476A lies within the extracellular domain of the Alk protein (UniProt.org). V476A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
L1198F missense gain of function ALK L1198F lies within the protein kinase domain of the Alk protein (UniProt.org). L1198F confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation (PMID: 21596819).
G746C missense unknown ALK G746C does not lie within any known functional domains of the Alk protein (UniProt.org). G746C has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
S1053F missense unknown ALK S1053F lies within the helical domain of the Alk protein (UniProt.org). S1053F has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
A1266D missense unknown ALK A1266D lies within the protein kinase domain of the Alk protein (UniProt.org). A1266D has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
F1174V missense gain of function - predicted ALK F1174V lies within the protein kinase domain of the Alk protein (UniProt.org). F1174V is predicted to confer a gain of function to the Alk protein as indicated by constitutive activation of the Alk protein in cell culture (PMID: 21242967) and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 24675041). Y
L1196Q missense gain of function - predicted ALK L1196Q lies within the protein kinase domain of the Alk protein (UniProt.org). L1196Q is predicted to confer a gain of function on the Alk protein as indicated by increased phosphorylation of Alk (PMID: 25749034) and has been demonstrated to confer resistance to Alk inhibitors in the context of NPM1-ALK in culture (PMID: 25749034, PMID: 23239810). Y
M1478T missense unknown ALK M1478T lies within the cytoplasmic domain of the Alk protein (UniProt.org). M1478T has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
T1151dup duplication unknown ALK T1151dup indicates the insertion of the duplicate amino acid, threonine (T)-1151, in the protein kinase domain of the Alk protein (UniProt.org). T1151dup has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 22277784, PMID: 20695522), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
G1202R missense unknown ALK G1202R lies within the protein kinase domain of the Alk protein (UniProt.org). G1202R has been demonstrated to promote secondary drug resistance in the context of EML4-ALK (PMID: 22277784, PMID: 24736079), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
T429I missense unknown ALK T429I lies within the extracellular domain of the Alk protein (UniProt.org). T429I has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
D94N missense unknown ALK D94N lies within the extracellular domain of the Alk protein (UniProt.org). D94N has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
S1206C missense unknown ALK S1206C lies within the protein kinase domain of the Alk protein (UniProt.org). S1206C has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25421750), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
D1203fs frameshift loss of function - predicted ALK D1203fs results in a change in the amino acid sequence of the Alk protein beginning at aa 1203 of 1620, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the ATP binding site, D1203fs is predicted to lead to a loss of Alk protein function (UniProt.org).
I1250T missense loss of function ALK I1250T lies within the protein kinase domain of the Alk protein (UniProt.org). I1250T confers a loss of function on Alk as indicated by loss of kinase activity and loss of the ability to activate downstream signaling pathways in cell culture (PMID: 21804922).
T1151M missense unknown ALK T1151M lies within the protein kinase domain and inhibitor binding region of the Alk protein (UniProt.org). T1151M has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 27009859), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
M552I missense no effect - predicted ALK M552I lies within the MAM domain 2 of the Alk protein (UniProt.org). M552I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
S865P missense no effect - predicted ALK S865P does not lie within any known functional domains of the Alk protein (UniProt.org). S865P has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
C1156Y missense unknown ALK C1156Y lies within the protein kinase domain of the Alk protein (UniProt.org). C1156Y has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 21613408, PMID: 20979473, PMID: 27490033), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
fusion fusion unknown ALK fusion indicates a fusion of the ALK gene, but the fusion partner is unknown.
P40L missense unknown ALK P40L lies within the extracellular domain of the Alk protein (UniProt.org). P40L has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018).
E862D missense unknown ALK E862D does not lie within any known functional domains of the Alk protein (UniProt.org). E862D has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
V66G missense unknown ALK V66G lies within the extracellular domain of the Alk protein (UniProt.org). V66G has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
P1543S missense unknown ALK P1543S lies within the cytoplasmic domain of the Alk protein (UniProt.org). P1543S has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
D1529E missense no effect - predicted ALK D1529E lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1529E has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
F1174S missense gain of function ALK F1174S lies within the protein kinase domain of the Alk protein (UniProt.org). F1174S results in ligand-independent activation of the Alk protein, increased Erk phosphorylation, and transformation of cells in culture (PMID: 21059859).
V1413G missense unknown ALK V1413G lies within the cytoplasmic domain of the Alk protein (UniProt.org). V1413G has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
F1245C missense gain of function ALK F1245C lies within the protein kinase domain of the Alk protein (UniProt.org). Alk F1245C results in increased downstream signalling and is transforming in cell culture (PMID: 21838707).
F1245I missense unknown ALK F1245I lies within the protein kinase domain of the Alk protein (UniProt.org). F1245I has not been characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
L1198V missense unknown ALK L1198V lies within the protein kinase domain of the Alk protein (UniProt.org). L1198V has been demonstrated to confer resistance to ALK inhibitors in vivo in the context of EML4-ALK and ALK F1174L (PMID: 29636358), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2018). Y
S529Y missense no effect - predicted ALK S529Y lies within the MAM domain 2 of the Alk protein (UniProt.org). S529Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
act mut unknown gain of function ALK act mut indicates that this variant results in a gain of function in the Alk protein. However, the specific amino acid change has not been identified.
M1166V missense unknown ALK M1166V lies within the protein kinase domain of the Alk protein (UniProt.org). M1166V has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
negative unknown loss of function ALK negative indicates a lack of the ALK gene, mRNA, and/or protein.
V198M missense unknown ALK V198M lies within the extracellular domain of the Alk protein (UniProt.org). V198M has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2018).
G1269E missense unknown ALK G1269E lies within the protein kinase domain of the Alk protein (UniProt.org). G1269E has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
mutant unknown unknown ALK mutant indicates an unspecified mutation in the ALK gene.
G1123D missense unknown ALK G1123D lies within the protein kinase domain of the Alk protein (UniProt.org). G1123D has been demonstrated to occur as a secondary drug resistance mutation in culture (PMID: 21948233), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
L1204V missense unknown ALK L1204V lies within the protein kinase domain of the Alk protein (UniProt.org). L1204V has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 29650534), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
K1491R missense no effect - predicted ALK K1491R lies within the cytoplasmic domain of the Alk protein (UniProt.org). K1491R has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
P1112Q missense unknown ALK P1112Q does not lie within any known functional domains of the Alk protein (UniProt.org). P1112Q has not been characterized in the scientific literature and therefore, its effect on Alk protein function is unknown (PubMed, Sep 2018).
G1128S missense unknown ALK G1128S lies within the protein kinase domain of the Alk protein (UniProt.org). G1128S has been demonstrated to occur as a secondary drug resistance mutation in the context of NPM1-ALK (PMID: 25749034), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jun 2018). Y
M301I missense no effect - predicted ALK M301I lies within the MAM domain 2 of the Alk protein (UniProt.org). M301I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
T680I missense no effect - predicted ALK T680I lies within the MAM domain 2 of the Alk protein (UniProt.org). T680I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
H354Q missense no effect - predicted ALK H354Q lies within the MAM domain 1 of the Alk protein (UniProt.org). H354Q has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Alk (PMID: 29533785) and therefore, is predicted to have no effect on Alk protein function.
G1269S missense gain of function - predicted ALK G1269S lies within the protein kinase domain of the Alk protein (UniProt.org). G1269S is predicted to confer a gain of function on the Alk protein as indicated by increased phosphorylation of Alk (PMID: 21948233) and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK (PMID: 21948233, PMID: 22034911). Y
F1245V missense unknown ALK F1245V lies within the protein kinase domain of the Alk protein (UniProt.org). F1245V has been identified in the scientific literature (PMID: 28183697), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Oct 2018).
Molecular Profile Protein Effect Treatment Approaches
ALK E1303K unknown
ALK G1137R no effect - predicted
ALK D1249fs loss of function - predicted
ALK V163L unknown
EML4-ALK ALK C1156Y ALK F1174I
NPM1-ALK ALK F1174I Alectinib Brigatinib Ceritinib Crizotinib Lorlatinib
ALK F1174I gain of function ALK Inhibitor
ALK R1113Q unknown
EML4-ALK ALK C1156Y ALK F1174C
EML4-ALK ALK F1174C Brigatinib Lorlatinib
EML4-ALK ALK F1174C ALK G1269A
ALK F1174C gain of function ALK Inhibitor
EML4-ALK ALK F1174C ALK L1198F Crizotinib
EML4-ALK ALK L1196M ALK F1174C
EML4-ALK ALK D1203N ALK F1174C
NPM1-ALK ALK L1196M ALK D1203N ASP3026
ALK rearrange ALK E1210K ALK D1203N ALK G1269A
EML4-ALK ALK D1203N ALK E1210K Lorlatinib
EML4-ALK ALK C1156Y ALK D1203N
NPM1-ALK ALK C1156F ALK D1203N
EML4-ALK ALK D1203N Alectinib Brigatinib Ceritinib Lorlatinib
ALK rearrange ALK I1171N ALK D1203N
ALK D1203N unknown
ALK E994K no effect - predicted
ALK A1266V no effect - predicted
NPM1-ALK ALK G1269A ASP3026 AZD3463 Brigatinib
EML4-ALK ALK G1269A ALK I1171N
EML4-ALK ALK L1198F ALK G1269A Brigatinib Crizotinib
ALK rearrange ALK T1151dup ALK G1269A
ALK rearrange ALK G1202R ALK G1269A ALK L1204V
ALK fusion ALK G1269A
ALK G1269A unknown
EML4-ALK ALK C1156Y ALK G1269A
EML4-ALK ALK G1269A ALK I1171T
EML4-ALK ALK G1269A ALK L1196M
EML4-ALK ALK G1269A Alectinib AZD3463 Brigatinib Ceritinib Lorlatinib
ALK rearrange ALK G1202R ALK G1269A
ALK K1062M gain of function ALK Inhibitor
ALK L1122V unknown
NPM1-ALK ALK L1122V
NPM1-ALK ALK L1122V ALK L1196M
ALK I1461V unknown
ALK R401Q no effect - predicted
ALK amp ALK F1174L
ALK amp EML4-ALK EGFR L858R
ALK amp Tp53 wild-type
ALK amp ALK F1174V
ALK amp no effect
ALK amp ALK rearrange
NPM1-ALK amp
ALK A195V no effect - predicted
ALK D1091N unknown
ALK V1545I no effect - predicted
ALK A585T no effect - predicted
ALK A1200V no effect - predicted
EML4-ALK ALK G1202del Lorlatinib
ALK G1202del unknown
EML4-ALK ALK L1152P Brigatinib
ALK L1152P unknown
ALK F1245L unknown
ALK G689V unknown
ALK L1152R unknown
ALK fusion ALK L1152R
EML4-ALK ALK L1152R Brigatinib Lorlatinib
ALK C990R unknown
EML4-ALK ALK V1180L ASP3026 Brigatinib Ceritinib Lorlatinib TAE684
ALK V1180L unknown
ALK I1179V unknown
EML4-ALK ALK L1196M ALK I1179V
EML4-ALK ALK F1174V ALK I1171S
EML4-ALK ALK I1171S Lorlatinib
ALK I1171S unknown
NPM1-ALK ALK I1171S AZD3463 Brigatinib
EML4-ALK ALK L1196M ALK I1171S
ALK P336S no effect - predicted
ALK P1139S unknown
NPM1-ALK ALK P1139S Alectinib ASP3026 Brigatinib Crizotinib
ALK F1174L ALK L1198P
EML4-ALK ALK L1198P
ALK L1198P gain of function - predicted ALK Inhibitor
ALK rearrange ALK L1196M
ALK rearrange ALK mut
ALK rearrange SRC pos
ALK rearrange ALK I1171T
ALK rearrange ALK I1171N
ALK rearrange RB1 C706F TP53 loss
ALK rearrange ALK G1202R ALK L1196M
ALK rearrange ALK S1206Y
ALK rearrange ALK C1156Y ALK L1198F
ALK rearrange ALK C1156Y
ALK rearrange MAP2K1 K57N
ALK rearrange ALK G1202R
ALK rearrange unknown ALK Inhibitor
ALK rearrange MET amp
ALK rearrange ALK I1171N ALK L1198F
ALK G1123S ALK rearrange
ALK V66A unknown
ALK S1206Y unknown
EML4-ALK ALK S1206Y Brigatinib Ceritinib Lorlatinib
ALK fusion ALK S1206Y
ALK R1212H unknown
ALK R1192P gain of function ALK Inhibitor
NPM1-ALK ALK R1192P Brigatinib
EML4-ALK ALK R1192P Alectinib AZD3463 Brigatinib Crizotinib
ALK F1174L ALK G1123S
ALK G1123S unknown
ALK P1298S unknown
ALK R1209Q loss of function - predicted
EML4-ALK ALK C1156Y ALK I1171T
NPM1-ALK ALK I1171T
EML4-ALK ALK I1171T Ceritinib Lorlatinib TAE684
ALK I1171T gain of function
ALK R1275Q TP53 wild-type
ALK R1275Q gain of function ALK Inhibitor
ALK R1275L unknown
NPM1-ALK ALK C1156F Crizotinib
ALK C1156F unknown
ALK G1552R no effect - predicted
ALK G875R no effect - predicted
ALK Y1278S gain of function ALK Inhibitor
ALK G922R unknown
ALK F457L no effect - predicted
ALK P1599S unknown
ALK P858S no effect - predicted
ALK F1245Q unknown
ALK H1030P unknown
ALK N1178H unknown
NPM1-ALK ALK N1178H Alectinib Crizotinib
ALK L560F no effect - predicted
ALK D1529G unknown
EML4-ALK ALK I1171N Brigatinib Ceritinib Lorlatinib
ALK I1171N gain of function ALK Inhibitor
NPM1-ALK ALK I1171N
ALK R311H unknown
ALK P36S unknown
ALK R133H no effect - predicted
EML4-ALK ALK S1206F Brigatinib
ALK S1206F unknown
NPM1-ALK ALK L1196M Brigatinib Ceritinib
NPM1-ALK ALK L1196M ALK S1206C
EML4-ALK ALK L1196M ALK F1174V
EML4-ALK ALK L1196M ALK L1256F
EML4-ALK ALK C1156Y ALK L1196M
ALK L1196M gain of function - predicted ALK Inhibitor
EML4-ALK ALK L1196M ALK G1202R
EML4-ALK ALK L1196M ALK L1198H
EML4-ALK ALK L1196M ALK F1174L
ALK fusion ALK L1196M
EML4-ALK ALK L1196M ALK L1198F
EML4-ALK ALK L1196M Brigatinib Ceritinib Ensartinib Entrectinib Lorlatinib Ropotrectinib
ALK E717K unknown
ALK R753Q unknown
ALK K894T unknown
ALK W501* loss of function - predicted
EML4-ALK ALK E1210K ALK S1206C
EML4-ALK ALK E1210K Alectinib Brigatinib Ceritinib Lorlatinib
ALK E1210K unknown
NPM1-ALK ALK E1210K Crizotinib
ALK wild-type no effect
ALK wild-type TP53 wild-type
ALK wild-type TP53 P177T
ALK wild-type TP53 mutant
ALK wild-type EGFR wild-type
ALK wild-type TP53 H168R
ALK wild-type TP53 C176F
ALK positive unknown
ALK G1128A gain of function ALK Inhibitor
ALK M1166R gain of function ALK Inhibitor
ALK L1256F unknown
EML4-ALK ALK C1156Y ALK L1256F
ALK S711R no effect - predicted
ALK L1198H unknown
ALK G1201E gain of function ALK Inhibitor
ALK A1047T unknown
ALK L868Q unknown
ALK F1174L ALK G1123D
EML4-ALK ALK F1174L Alectinib AZD3463 Lorlatinib
NPM1-ALK ALK F1174L Brigatinib
ALK F1174L TP53 wild-type
ALK F1174L gain of function ALK Inhibitor
EML4-ALK ALK F1174L ALK L1198V
ALK V476A no effect - predicted
ALK L1198F gain of function ALK Inhibitor
NPM1-ALK ALK F1174V ALK L1198F Crizotinib
EML4-ALK ALK C1156Y ALK L1198F Crizotinib
EML4-ALK ALK L1198F Brigatinib Crizotinib
NPM1-ALK ALK L1198F Crizotinib
EML4-ALK ALK L1198F ALK G1202R Crizotinib
ALK G746C unknown
ALK S1053F unknown
ALK A1266D unknown
EML4-ALK ALK F1174V ALK G1202R
ALK F1174V gain of function - predicted ALK Inhibitor
NPM1-ALK ALK F1174V Brigatinib Ceritinib Crizotinib
EML4-ALK ALK F1174V Alectinib Brigatinib
EML4-ALK ALK C1156Y ALK F1174V
NPM1-ALK ALK L1196Q ASP3026
ALK L1196Q gain of function - predicted ALK Inhibitor
ALK M1478T unknown
ALK T1151dup unknown
EML4-ALK ALK T1151dup Brigatinib
ALK fusion ALK T1151dup
EML4-ALK ALK G1202R Brigatinib Lorlatinib
ALK fusion ALK G1202R
ALK G1202R unknown
ALK T429I unknown
ALK D94N unknown
ALK S1206C unknown
NPM1-ALK ALK S1206C
ALK D1203fs loss of function - predicted
ALK I1250T loss of function
EML4-ALK ALK T1151M Alectinib AZD3463 Brigatinib Crizotinib
NPM1-ALK ALK T1151M
ALK T1151M unknown
ALK M552I no effect - predicted
ALK S865P no effect - predicted
NPM1-ALK ALK C1156Y
ALK fusion ALK C1156Y
EML4-ALK ALK C1156Y Alectinib Brigatinib Ensartinib Lorlatinib
ALK C1156Y unknown
ALK fusion unknown ALK Inhibitor
ALK fusion SRC over exp
ALK P40L unknown
ALK E862D unknown
ALK V66G unknown
ALK P1543S unknown
ALK D1529E no effect - predicted
ALK F1174S gain of function ALK Inhibitor
ALK V1413G unknown
EML4-ALK ALK F1245C Ceritinib
ALK F1245C TP53 wild-type
ALK F1245C gain of function ALK Inhibitor
ALK F1245I unknown
ALK L1198V unknown
ALK S529Y no effect - predicted
ALK act mut gain of function ALK Inhibitor
ALK act mut TP53 wild-type
ALK M1166V unknown
ALK neg ROS1 pos
ALK negative loss of function
ALK V198M unknown
ALK G1269E unknown
ALK mutant unknown
ALK mut TP53 wild-type
ALK G1123D unknown
ALK L1204V unknown
ALK K1491R no effect - predicted
ALK P1112Q unknown
ALK G1128S unknown
NPM1-ALK ALK G1128S Brigatinib
ALK M301I no effect - predicted
ALK T680I no effect - predicted
ALK H354Q no effect - predicted
ALK G1269S gain of function - predicted ALK Inhibitor
ALK F1245V unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4-ALK ALK C1156Y ALK F1174I Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174I were resistant to ASP3026 relative to wild type NPM1-ALK in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK with ALK F1174I were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
NPM1-ALK ALK F1174I Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174I in culture (PMID: 25749034). 25749034
EML4-ALK ALK C1156Y ALK F1174C Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK F1174C Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated decreased sensitivity to Alecensa (alectinib) in culture compared to cells expressing EML4-ALK with wild-type ALK (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 27432227 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 27432227 26698910
EML4-ALK ALK F1174C non-small cell lung carcinoma resistant Ceritinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who developed resistance to Xalkori (crizotinib) treatment was subsequently treated with Zykadia (ceritinib), eventually progressed, and was found to have acquired ALK F1174C (PMID: 24675041). 24675041
EML4-ALK ALK F1174C Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK F1174C Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor decreased response Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK F1174C Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). 27432227
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor decreased response Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
ALK rearrange ALK E1210K ALK D1203N ALK G1269A non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK C1156Y ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and D1203N were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with C1156F and D1203N were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and ALK D1203N were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and ALK D1203N were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and D1203N were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK with ALK C1156F and D1203N were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F and D1203N were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). 25749034
EML4-ALK ALK D1203N Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK D1203N Advanced Solid Tumor resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
EML4-ALK ALK D1203N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK rearrange ALK I1171N ALK D1203N non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N in cis developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
NPM1-ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing NPM1-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A anaplastic large cell lymphoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited the growth of transformed cells expressing NPM1-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1269A were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A ALK I1171N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
ALK rearrange ALK T1151dup ALK G1269A non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526). 25724526
ALK rearrange ALK G1202R ALK G1269A ALK L1204V non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK G1269A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
EML4-ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK G1269A ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK G1269A ALK L1196M non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087). 23344087
EML4-ALK ALK G1269A ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) modestly inhibited growth of transformed cells expression EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1269A Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor decreased response Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated a decreased response when treated with Entrectinib (RXDX-101) compared to cells expressing wild-type EML4-ALK (PMID: 26939704). 26939704
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of a Xalkori (crizotinib)-resistant human non-small cell lung cancer cell line harboring an EML-ALK fusion with ALK G1269A in culture and induced tumor regression in cell line xenograft models (PMID: 26849637, PMID: 23344087). 26849637 23344087
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive Alectinib Clinical Study Actionable In a clinical case study, a patient with EML4-ALK fusion positive non-small cell lung cancer with ALK G1269A had a partial response to Alecensa (alectinib) treatment (PMID: 26849637). 26849637
EML4-ALK ALK G1269A non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated stable disease when treated with Xalkori (crizotinib), but then progressed, and was found to harbor a secondary resistance mutation, ALK G1269A (PMID: 22235099). 22235099
EML4-ALK ALK G1269A non-small cell lung carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human lung cancer cell lines expressing ALK G1269A in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human lung cancer cell lines harboring EML4-ALK with ALK G1269A demonstrated sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK G1269A non-small cell lung carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315). 26144315
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In preclinical studies, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859, PMID: 26698910). 26698910 27009859
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK in the context of EML4-ALK were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22235099). 22235099
EML4-ALK ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M anaplastic large cell lymphoma resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
ALK amp ALK F1174L neuroblastoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK amp ALK F1174L neuroblastoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK amp EML4-ALK EGFR L858R non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK partially responded to Xalkori (crizotinib) therapy, but progressed after four months, and was found to have acquired ALK amplification and EGFR L858R (PMID: 23344087). 23344087
ALK amp Tp53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). 26438783
ALK amp ALK F1174V neuroblastoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK amp ALK F1174V neuroblastoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK amp neuroblastoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) was less efficient than Lorlatinib (PF-06463922) to induced growth inhibition in ALK-amplified neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK amp neuroblastoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of ALK amplified neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK amp neuroblastoma sensitive CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 22203728). 22203728
ALK amp ALK rearrange non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, two non-small cell lung carcinoma patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and was found to have acquired ALK amplification (PMID: 25724526). 25724526
ALK amp ALK rearrange non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, three patients with non-small cell lung carcinoma co-harboring an ALK rearrangement and ALK amplification demonstrated resistance to Xalkori (crizotinib) treatment (PMID: 27432227). 27432227
NPM1-ALK amp anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma decreased response Alectinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK demonstrated a decreased response compared to parental cell lines harboring NPM1-ALK when treated with Alecensa (alectinib) in culture (PMID: 25421750). 25421750
NPM1-ALK amp anaplastic large cell lymphoma resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring an amplification of NPM1-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
ALK D1091N neuroblastoma predicted - sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) treatment in a neuroblastoma cell line harboring ALK D1091N resulted in decreased cell viability, inhibition of colony formation, and inhibition of Pi3k pathway signaling in culture (PMID: 28455243). 28455243
ALK D1091N neuroblastoma predicted - sensitive Alectinib + Doxorubicin Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). 28455243
ALK D1091N neuroblastoma sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 treatment in a neuroblastoma cell line harboring ALK D1091N resulted in inhibition of colony formation, repression of Pi3k signaling, and induction of apoptosis in culture (PMID: 26786851). 26786851
ALK D1091N neuroblastoma sensitive AZD3463 + Doxorubicin Preclinical - Cell culture Actionable In a preclinical study, AZD3463 treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). 28455243
EML4-ALK ALK G1202del Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Alunbrig (brigatinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated moderate resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202del Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK L1152P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152P in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152P Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152P Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK L1152R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK L1152R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21791641). 21791641
EML4-ALK ALK L1152R non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a response to Xalkori (crizotinib) treatment, but after 3 months showed tumor progression, and was found to harbor the secondary resistance mutation, ALK L1152R (PMID: 21791641). 21791641
EML4-ALK ALK L1152R Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK V1180L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing ALK V1180L in the context of EML4-ALK in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L non-small cell lung carcinoma resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK ALK V1180L in culture (PMID: 25228534). 25228534
EML4-ALK ALK V1180L non-small cell lung carcinoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK V1180L non-small cell lung carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring ALK V1180L in the context of EML4-ALK was resistant to Xalkori (crizotinib) treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK L1196M ALK I1179V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK F1174V ALK I1171S non-small cell lung carcinoma resistant Alectinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158). 26464158
EML4-ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859), however, another study with comparable cells demonstrated sensitivity (PMID: 27432227). 27432227 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859), however, in another study comparable cells demonstrated sensitivity (PMID: 27432227). 27009859 27432227
EML4-ALK ALK I1171S Advanced Solid Tumor resistant AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK I1171S Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171S non-small cell lung carcinoma resistant Alectinib Clinical Study Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib) but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796). 25393796
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing NPM1-ALK with ALK I1171S in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S anaplastic large cell lymphoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1161S were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK I1171S Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK I1171S in culture (PMID: 27009859). 27009859
EML4-ALK ALK L1196M ALK I1171S Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK P1139S Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK P1139S in the context of NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S in culture (PMID: 25421750). 25421750
NPM1-ALK ALK P1139S Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK P1139S in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1198P Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233). 21948233
EML4-ALK ALK L1198P Advanced Solid Tumor resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
ALK L1198P neuroblastoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to Xalkori (crizotinib) in culture (PMID: 21948233). 21948233
ALK L1198P neuroblastoma resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, overexpression of ALK L1198P in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
ALK rearrange ALK L1196M non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
ALK rearrange ALK L1196M non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, four non-small cell lung carcinoma patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and was found to have acquired ALK L1196M (PMID: 25724526). 25724526
ALK rearrange ALK mut non-small cell lung carcinoma sensitive Ceritinib Clinical Study Actionable In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer that acquired ALK drug resistance mutations following Xalkori (crizotinib) treatment had a median progression-free survival (mPFS) of 5.4 months on Zykadia (ceritinib), which was not significantly different than the mPFS of 6.5 months for patients without ALK mutations (PMID: 25724526). 25724526
ALK rearrange SRC pos non-small cell lung carcinoma sensitive Saracatinib + Ceritinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Saracatinib (AZD0530) and Zykadia (ceritinib) demonstrated efficacy in non-small cell lung cancer patient derived cells harboring an ALK fusion and upregulation of SRC in culture (PMID: 25394791). 25394791
ALK rearrange ALK I1171T lung adenocarcinoma resistant Alectinib Clinical Study Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T lung adenocarcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement and ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171N non-small cell lung carcinoma predicted - resistant Alectinib Clinical Study Actionable In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911). 27565911
ALK rearrange RB1 C706F TP53 loss lung small cell carcinoma predicted - resistant Lorlatinib Clinical Study Actionable In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). 28285684
ALK rearrange ALK G1202R ALK L1196M non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, ALK L1196M was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK S1206Y non-small cell lung carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK S1206Y in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
ALK rearrange ALK S1206Y non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). 25724526
ALK rearrange ALK C1156Y ALK L1198F non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, ALK D1203N was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
ALK rearrange ALK C1156Y non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 18.2 months, and was found to have acquired ALK C1156Y (PMID: 25724526). 25724526
ALK rearrange MAP2K1 K57N non-small cell lung carcinoma sensitive Ceritinib + Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of AZD6244, resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). 25394791
ALK rearrange ALK G1202R non-small cell lung carcinoma predicted - resistant Alectinib Clinical Study Actionable In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Xalkori (crizotinib) followed by Alecensa (alectinib) therapy (PMID: 27130468). 27130468
ALK rearrange ALK G1202R non-small cell lung carcinoma predicted - resistant Alectinib Clinical Study Actionable In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Zykadia (ceritinib) followed by Alecensa (alectinib) therapy (PMID: 28285684). 28285684
ALK rearrange non-small cell lung carcinoma sensitive Ensartinib Phase Ib/II Actionable In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months (PMID: 29563138; NCT01625234). 29563138
ALK rearrange non-small cell lung carcinoma sensitive Ensartinib Clinical Study Actionable In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Ensartinib (X-396), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma no benefit Nivolumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma no benefit Nivolumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Afatinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange Advanced Solid Tumor sensitive ASP3026 Phase I Actionable In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192). 26966027
ALK rearrange non-small cell lung carcinoma no benefit Osimertinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive Alectinib Phase II Actionable In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747). 26598747
ALK rearrange non-small cell lung carcinoma sensitive Alectinib FDA approved Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840). 28586279
ALK rearrange non-small cell lung carcinoma sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as the preferred first-line therapy for patients with ALK-rearranged, metastatic non-small cell lung cancer, and as the subsequent therapy for patients who have progressed after Xalkori (crizotinib) (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive Alectinib Clinical Study Actionable In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alecensa (alectinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive Ceritinib + Crizotinib Clinical Study Actionable In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526). 25724526
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Phase Ib/II Actionable In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in crizotinib-treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716). 27836716
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as subsequent therapy for ALK rearranged non-small cell lung cancer patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Clinical Study Actionable In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib FDA approved Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). 28475456
ALK rearrange non-small cell lung carcinoma sensitive Brigatinib Clinical Study Actionable In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulted in objective response in 17% (3/18) and stable disease in 50% (9/18) of patients with alectinib-refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). 29935304
ALK rearrange non-small cell lung carcinoma no benefit Durvalumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma no benefit Durvalumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 48% (103/215, 4% complete response, 44% partial response) in ALK-rearranged non-small cell lung carcinoma patients received more than one prior Alk kinase inhibitor therapy, with an estimated median response duration of 12.5 months (J Clin Oncol, May 2018, 36(no. 15_suppl):9032-9032; NCT01970865). detail...
ALK rearrange non-small cell lung carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorlatinib (PF-06463922) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). 29074098
ALK rearrange non-small cell lung carcinoma sensitive Crizotinib Phase III Actionable In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). 27022118
ALK rearrange non-small cell lung carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line and subsequent therapy for ALK rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive Crizotinib Phase III Actionable In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). detail...
ALK rearrange non-small cell lung carcinoma sensitive Crizotinib FDA approved Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). 25470694
ALK rearrange non-small cell lung carcinoma no benefit Gefitinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Erlotinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Atezolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma no benefit Atezolizumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma no benefit Pembrolizumab Clinical Study Actionable In a retrospective study, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange non-small cell lung carcinoma no benefit Pembrolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange Advanced Solid Tumor sensitive Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007). detail...
ALK rearrange Advanced Solid Tumor sensitive Entrectinib Phase I Actionable In a clinical study analyzing combined results of 2 Phase I trials, Entrectinib (RXDX-101) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients received prior Alk inhibitor treatments (PMID: 28183697). 28183697
ALK rearrange non-small cell lung carcinoma sensitive Ceritinib Clinical Study Actionable In a retrospective study, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated a median overall survival of 49.5 months following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Zykadia (ceritinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange non-small cell lung carcinoma sensitive Ceritinib Phase II Actionable In a Phase II trial (ASCEND-2), non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement and previously treated with Xalkori (crizotinib) and chemotherapy demonstrated an overall response rate of 38.6% (54/140), a disease control rate of 77.1%, a median time to response of 1.8 months, a median duration of response of 9.7 months, and a median progression-free survival of 5.7 months when treated with Zykadia (ceritinib) (PMID: 27432917; NCT01685060). 27432917
ALK rearrange non-small cell lung carcinoma sensitive Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer patients, and as subsequent therapy in patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org). detail...
ALK rearrange non-small cell lung carcinoma sensitive Ceritinib FDA approved Actionable In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). 25754348
ALK rearrange non-small cell lung carcinoma sensitive Ceritinib Phase III Actionable In a Phase III trial, first-line treatment with Zykadia (ceritinib) resulted in an improved median progression-free survival of 16.6 months, compared to 8.1 months with chemotherapy, in patients with ALK-rearranged non-squamous non-small cell lung cancer (PMID: 28126333; NCT01828099). 28126333
ALK rearrange MET amp lung adenocarcinoma resistant Alectinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring an ALK rearrangement developed resistance to Alecensa (alectinib)treatment, and subsequently was found to harbor amplification of MET (PMID: 24128725, PMID: 24518097). 24518097 24128725
ALK rearrange MET amp lung adenocarcinoma sensitive Crizotinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring an ALK rearrangement who developed resistance to Alecensa (alectinib) likely due to acquisition of MET amplification, responded well to treatment with Xalkori (crizotinib), demonstrating a radiological response after 12 days (PMID: 24128725, PMID: 24518097). 24128725 24518097
ALK rearrange ALK I1171N ALK L1198F non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534). 29650534
ALK G1123S ALK rearrange lung adenocarcinoma predicted - sensitive Alectinib Clinical Study Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired an ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
ALK G1123S ALK rearrange lung adenocarcinoma predicted - resistant Ceritinib Clinical Study Actionable In a clinical study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). 26134233
EML4-ALK ALK S1206Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing S1206Y in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK S1206Y Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated growth inhibition with Zykadia (ceritinib) treatment in culture (PMID: 24675041). 24675041
EML4-ALK ALK S1206Y non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, an ALK S1206Y secondary mutation in the context of EML4-ALK was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer, and resistance was replicated in cell culture studies (PMID: 22277784). 22277784
EML4-ALK ALK S1206Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). 26144315
ALK R1192P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
NPM1-ALK ALK R1192P Advanced Solid Tumor decreased response AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P had a reduced response to AZD3463 mediated growth inhibition in culture compared to cells expressing wild-type NPM1-ALK (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P anaplastic large cell lymphoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK R1192P were resistant to Xalkori (crizotinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK R1192P Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK R1192P were resistant to Xalkori (Crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK R1192P Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells overexpressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
ALK G1123S neuroblastoma resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, overexpression of ALK G1123S in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
EML4-ALK ALK C1156Y ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T anaplastic large cell lymphoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, an anaplastic large-cell lymphoma cell line expressing ALK I1171T in the context of NPM1-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24509625). 24509625
NPM1-ALK ALK I1171T Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171T were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171T anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1171T were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
EML4-ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534), however, another study with comparable cells demonstrated sensitivity in culture (PMID: 27432227). 25228534 27432227
EML4-ALK ALK I1171T Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171T non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798). 25393798
EML4-ALK ALK I1171T Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T non-small cell lung carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4-ALK ALK I1171T Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534). 25228534
EML4-ALK ALK I1171T Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171T Advanced Solid Tumor sensitive TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534). 25228534
ALK I1171T ganglioneuroblastoma predicted - sensitive Ceritinib Clinical Study Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in a 43.6% decrease of the primary tumor after 6.5 months of treatment, and complete resolution of metastases at 21 months after initiation of treatment in a pediatric patient with ganglioneuroblastoma (PMID: 29907598). 29907598
ALK R1275Q neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783). 26438783
ALK R1275Q neuroblastoma sensitive CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 22203728). 22203728
ALK R1275Q neuroblastoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and irapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma conflicting Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK R1275Q in culture, and only delayed tumor growth in cell line xenograft models (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). 29907598
ALK R1275Q Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK R1275Q in culture (PMID: 26554404). 26554404
ALK R1275Q neuroblastoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). 29907598
ALK R1275Q Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, a transformed cell line expressing ALK R1275Q was sensitive to Alunbrig (brigatinib) in culture and in cell line xenograft models, resulting in cell growth inhibition (PMID: 27049722). 27049722
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK C1156F in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK C1156F were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK C1156F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK C1156F were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
ALK Y1278S Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK Y1278S was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
NPM1-ALK ALK N1178H Advanced Solid Tumor decreased response ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK N1178H in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK N1178H were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK N1178H were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK N1178H Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK N1178H in culture (PMID: 25749034). 25749034
EML4-ALK ALK I1171N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N non-small cell lung carcinoma resistant Alectinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798). 25393798
EML4-ALK ALK I1171N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK I1171N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
ALK I1171N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
NPM1-ALK ALK I1171N anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK I1171N were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Xalkori (critzotinb) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK I1171N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK I1171N were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
EML4-ALK ALK S1206F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853). 27780853
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical trial, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1196M ALK F1174V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK L1196M lung adenocarcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473). 20979473
EML4-ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK L1196M Advanced Solid Tumor sensitive Ropotrectinib Preclinical - Cell culture Actionable In a preclinical study, TPX-0005 inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4-ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK F1174L Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504). 21502504
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated decreased sensitivity to Alecensa (alectinib) compared to cells expressing EML4-ALK with wild-type ALK, in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing an EML4-ALK fusion and ALK L1196M in culture and in cell line xenograft models (PMID: 21575866). 21575866
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were sensitive to Entrectinib (RXDX-101), resulting in anti-proliferative activity in culture (PMID: 26939704). 26939704
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315). 26144315
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK L1196M demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910) 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 26698910 27432227
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4-ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were insensitive to Xalkori (crizotinib) as demonstrated by a lack of growth inhibition and Alk phosphorylation in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) inhibited cell survival and PI3K/AKT, MEK/ERK, and mTOR signaling in two human non-small cell lung carcinoma cell lines harboring the Xalkori (crizotinib) resistance mutation EML4-ALK ALK L1196M in culture and inhibited tumor growth in xenograft models of one of those cell lines (PMID: 24675041). 24675041
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408). 21613408
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ropotrectinib Preclinical - Cell culture Actionable In a preclinical study, TPX-0005 inhibited Alk activity and proliferation of transformed cells over expressing ALK L1196M in the context of EML4-ALK in culture (European Journal of Cancer , Volume 69, S32). detail...
EML4-ALK ALK E1210K ALK S1206C non-small cell lung carcinoma resistant Brigatinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C (PMID: 29636358). 29636358
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK E1210K non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358). 29636358
EML4-ALK ALK E1210K Advanced Solid Tumor conflicting Crizotinib Clinical Study Actionable In a clinical case study, a lung cancer patient harboring EML4-ALK demonstrated progression when treated with Xalkori (crizotinib) due to the secondary acquired resistance mutation, ALK E1210K, however, in vitro transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). 27432227
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK with ALK E1210K were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to Alunbrig (brigatinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK E1210K were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with E1210K were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK E1210K Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK E1210K in culture (PMID: 25749034). 25749034
ALK wild-type endometrial cancer no benefit dalantercept Phase II Actionable In a Phase II clinical trial, treatment with Dalantercept (ACE-041) did not demonstrate activity as single agent in recurrent or persistent endometrial cancer, with a median progression-free survival (PFS) of 2.1 months, overall survival of 14.5 months, no objective responses, and stable disease in 57% (16/28) of patients (PMID: 25888978). 25888978
ALK wild-type neuroblastoma resistant CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 22203728). 22203728
ALK wild-type melanoma sensitive Dalantercept + Doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, Dalantercept (ACE-041) in combination with Adria (doxorubicin) resulted in decreased tumor growth in cell line xenograft models of melanoma, with increased efficacy over either agent alone (PMID: 26373572). 26373572
ALK wild-type neuroblastoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 26554404). 26554404
ALK wild-type head and neck cancer predicted - sensitive Dalantercept + Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of Dalantercept (ACE-041) to Platinol (cisplatin) treatment resulted in increased cytoxicity and decreased tumor growth in cell line xenograft models of head and neck cancer (PMID: 26373572). 26373572
ALK wild-type Advanced Solid Tumor sensitive Ropotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0005 inhibited cell proliferation in transformed cell lines over expressing wild-type ALK in culture and suppressed tumor growth in xenograft models (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
ALK wild-type breast cancer predicted - sensitive Dalantercept + Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, Dalantercept (ACE-041) in combination with Platinol (cisplatin) resulted in decreased tumor growth in cell line xenograft models of breast cancer (PMID: 26373572). 26373572
ALK wild-type TP53 wild-type neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). 26438783
ALK wild-type TP53 P177T neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783). 26438783
ALK wild-type TP53 mutant neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). 26438783
ALK wild-type EGFR wild-type non-small cell lung carcinoma predicted - sensitive Cisplatin + Pembrolizumab + Pemetrexed FDA approved Actionable In a Phase III trial (KEYNOTE-189) that supported FDA approval, Keytruda (pembrolizumab) in combination with Alimta (pemetrexed), and a platinum therapy (cisplatin or carboplatin), resulted in improved overall survival rate at 12 months (69.2% vs 49.4%, HR=0.49, p<0.001) and median progression-free survival (8.8 vs 4.9 months, HR=0.52, p<0.001) compared to placebo in previously untreated metastatic nonsquamous non-small-cell lung cancer patients without EGFR or ALK mutations (PMID: 29658856; NCT02578680). 29658856
ALK wild-type EGFR wild-type non-small cell lung carcinoma predicted - sensitive Carboplatin + Pembrolizumab + Pemetrexed FDA approved Actionable In a Phase III trial (KEYNOTE-189) that supported FDA approval, Keytruda (pembrolizumab) in combination with Alimta (pemetrexed), and a platinum therapy (cisplatin or carboplatin), resulted in improved overall survival rate at 12 months (69.2% vs 49.4%, HR=0.49, p<0.001) and median progression-free survival (8.8 vs 4.9 months, HR=0.52, p<0.001) compared to placebo in previously untreated metastatic nonsquamous non-small-cell lung cancer patients without EGFR or ALK mutations (PMID: 29658856; NCT02578680). 29658856
ALK wild-type EGFR wild-type non-small cell lung carcinoma sensitive Atezolizumab + Bevacizumab + Carboplatin + Paclitaxel FDA approved Actionable In a Phase III trial (IMpower150) that supported FDA approval, Tecentriq (atezolizumab) in combination with bevacizumab, paclitaxel, and carboplatin resulted in significantly improved median progression-free survival (8.3 vs 6.8 months, HR=0.62, p<0.001) and median overall survival (19.2 vs 14.7 months, HR=0.78, p=0.02) compared to control in patients with metastatic nonsquamous non-small cell lung cancer, regardless of PD-L1 expression and EGFR or ALK mutation status (PMID: 29863955; NCT02366143). 29863955
ALK wild-type TP53 H168R neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783). 26438783
ALK wild-type TP53 C176F neuroblastoma no benefit Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783). 26438783
ALK positive non-small cell lung carcinoma sensitive Belizatinib Phase I Actionable In a Phase I clinical trial, Belizatinib (TSR-011) treatment resulted in a partial response in 60% (3/5) of non-small cell lung cancer patients positive for Alk (J Clin Oncol 32, 2014 (suppl; abstr e19005)). detail...
ALK positive non-small cell lung carcinoma sensitive Alectinib FDA approved Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in ALK-positive non-small cell lung cancer patients (PMID: 28586279; NCT02075840). 28586279
ALK positive non-small cell lung carcinoma sensitive Ensartinib Phase Ib/II Actionable In a Phase Ib/II trial, Ensartinib (X-396) treatment resulted in partial response (PR) in 60% (19/30) and stable disease in 7% (2/30) of ALK positive non-small cell lung carcinoma patients, PR was 88% (7/8) in crizotinib-naïve patients and 83% (10/12) in patients with prior crizotinib treatment (J Clin Oncol 34, 2016 (suppl; abstr 9056)). detail...
ALK positive neuroblastoma sensitive Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in partial response in a patient with ALK-positive neuroblastoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)). detail...
ALK positive non-small cell lung carcinoma sensitive Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in stable disease in a patient with ALK-positive non-small cell lung carcinoma (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)). detail...
ALK positive non-small cell lung carcinoma no benefit Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in ALK positive non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK positive non-small cell lung carcinoma sensitive Lorlatinib FDA approved Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 48% (97/198, 4% complete response, 44% partial response) in ALK positive non-small cell lung carcinoma patients received more than one prior Alk kinase inhibitor therapy, with an estimated median response duration of 12.5 months (J Clin Oncol, May 2018, 36(no. 15_suppl):9032-9032; NCT01970865). detail... detail...
ALK positive Advanced Solid Tumor sensitive Belizatinib Phase Ib/II Actionable In a Phase I trial, Belizatinib (TSR-011) treatment resulted in a response in 100% (3/3) of patients with ALK positive advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)). detail...
ALK G1128A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK G1128A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
EML4-ALK ALK C1156Y ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK F1174L Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174L in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) in culture (PMID: 27780853). 27780853
EML4-ALK ALK F1174L Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4-ALK ALK F1174L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing NPM1-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L anaplastic large cell lymphoma resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK F1174L were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK F1174L Advanced Solid Tumor resistant AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174L were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
ALK F1174L TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). 26438783
ALK F1174L neuroblastoma resistant Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1174L neuroblastoma sensitive CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture (PMID: 22203728). 22203728
ALK F1174L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1174L in culture (PMID: 26554404). 26554404
ALK F1174L neuroblastoma sensitive AZD3463 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3463 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture, resulted in near complete tumor regression in cell line xenograft models (PMID: 26786851). 26786851
ALK F1174L neuroblastoma sensitive Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
EML4-ALK ALK F1174L ALK L1198V non-small cell lung carcinoma resistant Brigatinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358). 29636358
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F anaplastic large cell lymphoma resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK F1174V and ALK L1198F were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK1198F were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V ALK L1198F Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK F1174V and ALK L1198F were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F non-small cell lung carcinoma resistant Lorlatinib Phase I Actionable In a Phase I clinical trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y ALK L1198F non-small cell lung carcinoma sensitive Crizotinib Clinical Study Actionable In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 27432227 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F Advanced Solid Tumor decreased response Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F had reduced sensitivity to growth inhibition mediated by Lorlatinib (PF-06463922) in comparison to EML4-ALK wild type in culture (PMID: 26698910). 26698910
NPM1-ALK ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1198F in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1198F were resistant to Zykadia (ceritinib) treatment in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK F1174V ALK G1202R non-small cell lung carcinoma sensitive Ceritinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041). 24675041
ALK F1174V neuroblastoma sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174V were sensitive to Alunbrig (brigatinib) in culture and in vivo, resulting in inhibition of both Alk activity and cell proliferation (PMID: 27049722). 27049722
NPM1-ALK ALK F1174V Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical trial, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor decreased response Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK F1174V Advanced Solid Tumor predicted - sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical trial, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK F1174V, but to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
EML4-ALK ALK F1174V Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174V in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK F1174V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK F1174V in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK F1174V non-small cell lung carcinoma sensitive Alectinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK initially responded to Xalkori (crizotinib), but then progressed due to acquisition of the secondary resistance mutation, ALK F1174V, and then responded to treatment with Alecensa (alectinib), demonstrating a complete response in one lung nodule and a 44% decrease in size in a second lung nodule (PMID: 26464158). 26464158
EML4-ALK ALK F1174V non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response to Xalkori (crizotinib) treatment after 3 months, but then progressed, and was found to harbor the secondary resistance mutation, ALK F1174V (PMID: 24736079). 24736079
EML4-ALK ALK C1156Y ALK F1174V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
NPM1-ALK ALK L1196Q anaplastic large cell lymphoma sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of human anaplastic large cell lymphoma cell lines harboring NPM1-ALK containing the crizotinib-resistant mutation ALK L1196Q in culture (PMID: 25749034). 25749034
NPM1-ALK ALK L1196Q anaplastic large cell lymphoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK containing ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). 25749034
EML4-ALK ALK T1151dup Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK T1151dup Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK T1151dup Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4-ALK ALK G1202R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4-ALK ALK G1202R non-small cell lung carcinoma predicted - resistant Alectinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK, who had developed resistance to Xalkori (crizotinib), was found to harbor ALK G1202R following treatment with Alecensa (alectinib) (PMID: 24736079). 24736079
EML4-ALK ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to RXDX-101 (PMID: 26939704). 26939704
EML4-ALK ALK G1202R non-small cell lung carcinoma resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were insensitive to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK G1202R non-small cell lung carcinoma resistant Ceritinib Clinical Study Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who acquired the secondary drug resistance mutation, ALK S1206Y, when treated with Xalkori (crizotinib) was subsequently treated with Zykadia (ceritinib), developed drug resistance, and was then found to have lost the ALK S1206Y mutation, but gained ALK G1202R (PMID: 24675041). 24675041
EML4-ALK ALK G1202R Advanced Solid Tumor sensitive Ropotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0005 inhibited Alk activity and proliferation of transformed cells over expressing ALK G1201R in the context of EML4-ALK in culture, resulted in tumor regression in cell line xenograft models (European Journal of Cancer , Volume 69, S32). detail...
EML4-ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4-ALK ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK G1202R non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, an ALK G1202R secondary mutation in the context of EML4-ALK was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer, and resistance was replicated in cell culture studies (PMID: 22277784). 22277784
EML4-ALK ALK G1202R lung cancer conflicting Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315). 26144315
EML4-ALK ALK G1202R lung cancer conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
ALK fusion ALK G1202R non-small cell lung carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK G1202R Advanced Solid Tumor sensitive Ropotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0005 inhibited ALK G1202R and suppressed tumor growth in cell line xenograft models with ALK G1202R (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
NPM1-ALK ALK S1206C Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK S1206C were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C anaplastic large cell lymphoma resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK ALK S1206C were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK S1206C were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK S1206C to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK ALK S1206C to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK S1206C Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK and ALK S1206C were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to ASP3026 in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4-ALK ALK T1151M Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M anaplastic large cell lymphoma resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK T1151M Advanced Solid Tumor resistant AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK T1151M were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
NPM1-ALK ALK C1156Y anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK C1156Y were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
EML4-ALK ALK C1156Y non-small cell lung carcinoma conflicting Ceritinib Clinical Study Actionable In a clinical study, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation C1156Y, did not respond to Zykadia (ceritinib) therapy (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y non-small cell lung carcinoma conflicting Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) demonstrated tumor growth inhibition in xenograft models of a human non-small cell lung cancer cell line harboring EML4-ALK with ALK C1156Y when compared to Xalkori (crizotinib) (PMID: 24675041). 24675041
EML4-ALK ALK C1156Y Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing ALK C1156Y in the context of EML4-ALK demonstrated minimal sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4-ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK ALK C1156Y were insensitive to Xalkori (crizotinib) as demonstrated by lack of growth inhibition and lack of kinase inhibition in culture (PMID: 21613408). 21613408
EML4-ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y non-small cell lung carcinoma resistant Luminespib Clinical Study Actionable In a clinical study, a patient with EML4-ALK positive non-small cell lung cancer with an ALK C1156Y secondary Xalkori (crizotinib) resistance mutation did not respond to Luminespib (AUY922) therapy (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK C1156Y (PMID: 21613408). 21613408
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were sensitive to Entrectinib (RXDX-101), resulting in anti-proliferative activity (PMID: 26939704). 26939704
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer developed resistance to Xalkori (crizotinib) with the emergence of ALK C1156Y, a secondary resistance mutation (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing EML4-ALK with ALK C1156Y were sensitive to Alecensa (alectinib) in culture (PMID: 21575866). 21575866
EML4-ALK ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4-ALK ALK C1156Y non-small cell lung carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I clinical study, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910). 26698910
ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical Actionable In a preclinical study, ALK C1156Y was sensitive to Alecensa (alectinib) in an in vitro enzyme assay (PMID: 21575866). 21575866
ALK fusion non-small cell lung carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK fusion non-small cell lung carcinoma sensitive Brigatinib Phase Ib/II Actionable In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716). 24091716
ALK fusion colorectal cancer sensitive Entrectinib Phase I Actionable In a Phase I clinical trial, Entrectinib (RXDX-101) treatment resulted in partial response for more than 3 months in a colorectal cancer patient harboring a CAD-ALK gene fusion (PMID: 26633560). 26633560
ALK fusion non-small cell lung carcinoma sensitive Alectinib Phase III Actionable In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)). detail...
ALK fusion non-small cell lung carcinoma sensitive Alectinib Phase II Actionable In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008)) detail...
ALK fusion anaplastic large cell lymphoma sensitive Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 83% (5/6, all complete responses), at the 165 mg dose, and 90% (18/20, with complete response in 80% (16/20), at the recommended phase 2 dose of 280 mg, in patients with anaplastic large cell lymphoma harboring an ALK fusion, with 72% of tested patients harboring NPM1-ALK (PMID: 28787259; NCT00939770). 28787259
ALK fusion Advanced Solid Tumor predicted - sensitive Ropotrectinib Phase I Actionable In a Phase I (TRIDENT-1) trial, Ropotrectinib (TPX-0005) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). detail...
ALK fusion inflammatory myofibroblastic tumor sensitive Crizotinib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Xalkori (crizotinib) resulted in an objective response rate of 86% (12/14), with complete response in 36% (5/14), in patients with inflammatory myofibroblastic tumor harboring an ALK fusion (PMID: 28787259; NCT00939770). 28787259
EML4-ALK ALK F1245C non-small cell lung carcinoma sensitive Ceritinib Clinical Study Actionable In a clinical study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 that demonstrated resistance to treatment with Xalkori (crizotinib) after acquisition of ALK F1245C, achieved a complete radiographic response with no evidence of progression at 6 months following treatment with Zykadia (ceritinib) (PMID: 26775591). 26775591
EML4-ALK ALK F1245C non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 demonstrated an initial response to treatment with Xalkori (crizotinib), but progressed after 27 months and was found to have acquired ALK F1245C (PMID: 26775591). 26775591
ALK F1245C TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). 26438783
ALK F1245C Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1245C neuroblastoma resistant Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C neuroblastoma sensitive Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1245C in culture (PMID: 26554404). 26554404
ALK act mut TP53 wild-type neuroblastoma predicted - sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). 26438783
ALK neg ROS1 pos non-small cell lung carcinoma sensitive Crizotinib Phase II Actionable In a Phase II trial, Xalkori (crizotinib) treatment resulted in an objective response rate of 69% (89/129), and a median duration of treatment of 7.8 months in ALK negative, ROS1 positive non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021). detail...
ALK negative non-small cell lung carcinoma resistant CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, ALK negative non-small cell lung carcinoma cells were resistant to CEP-28122 in culture and in cell line xenograft models (PMID: 22203728). 22203728
ALK negative colon carcinoma resistant CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, CEP-28122 did not inhibit tumor growth in cell line xenograft models of ALK-negative colon carcinoma (PMID: 22203728). 22203728
ALK negative leukemia resistant CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative leukemia cells in culture (PMID: 22203728). 22203728
ALK negative lymphoma resistant CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 did not inhibit growth of ALK-negative lymphoma cells in culture (PMID: 22203728). 22203728
ALK mut TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). 26438783
ALK G1123D neuroblastoma resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, overexpression of ALK G1123D in neuroblastoma cells harboring an ALK F1174L mutation resulted in resistance to TAE684 in culture (PMID: 21948233). 21948233
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Zykadia (ceritinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Alecensa (alectinib) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S anaplastic large cell lymphoma resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, human anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK G1128S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Lorlatinib (PF-06463922) in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to ASP3026 in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK G1128S in culture (PMID: 25749034). 25749034
NPM1-ALK ALK G1128S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK G1128S were resistant to Xalkori (crizotinib) in culture (PMID: 25749034). 25749034
ALK F1245V neuroblastoma sensitive Entrectinib Phase I Actionable In a Phase I trial, Entrectinib (RXDX-101) treatment resulted in partial response that lasted 8.3 months in a patient with neuroblastoma harboring ALK F1245V, who remained on treatment for over 3.5 years due to clinical benefit (PMID: 28183697). 28183697