Gene Detail

Gene Symbol MET
Synonyms AUTS9 | c-Met | DFNB97 | HGFR | RCCP2
Gene Description MET (c-MET), hepatocyte growth factor receptor, is a receptor tyrosine kinase, which activates MAPK, PI3K/AKT, SRC, and STAT pathways to promote cell proliferation, invasion and angiogenesis (PMID: 22128285). MET mutations have been identified in a variety of human cancers (PMID: 28603720).
Entrez Id 4233
Chromosome 7
Map Location 7q31.2
Canonical Transcript NM_000245

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
Y1003* nonsense gain of function MET Y1003* results in the formation of a stop codon in the juxtamembrane domain of the Met protein, which disrupts several splice enhancer sites (PMID: 25079552). Consequently, Y1003* results in exon skipping deletion of exon 14, increased Met kinase activity, and downstream Akt and Erk signaling (PMID: 25531467, PMID: 16397241).
Y1230D missense gain of function MET Y1230D (also referred to as MET Y1248D) lies within the protein kinase domain of the Met protein (UniProt.org). Y1230D (Y1248D) results in constitutive Met phosphorylation and is transforming in cell culture (PMID: 10327054).
H644Y missense no effect - predicted MET H644Y lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). H644Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
L707V missense unknown MET L707V lies within the IPT/TIG domain 2 of the Met protein (UniProt.org). L707V has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R417* nonsense loss of function - predicted MET R417* results in a premature truncation of the Met protein at amino acid 417 of 1390 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), R417* is predicted to lead to a loss of Met protein function.
E167K missense unknown MET E167K lies within the Sema domain of the Met protein (UniProt.org). E167K has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
Y321H missense unknown MET Y321H lies within the Sema domain of the Met protein (UniProt.org). Y321H has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
L238Yfs*25 frameshift loss of function - predicted MET L238Yfs*25 indicates a shift in the reading frame starting at amino acid 238 and terminating 25 residues downstream causing a premature truncation of the 1390 amino acid Met protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), L238Yfs*25 is predicted to lead to a loss of Met protein function.
P295H missense unknown MET P295H lies within the Sema domain of the Met protein (UniProt.org). P295H has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
T992I missense unknown MET T992I (also referred to as T1010I) lies within the cytoplasmic domain of the Met protein (UniProt.org). The functional effect of T992I is conflicting, as it has been reported both to have phosphorylation level and transforming capacity similar to wild-type Met protein (PMID: 20670955), and increase Met transforming capability and cell migration in culture (PMID: 14559814).
M118L missense unknown MET M118L lies within the Sema domain of the Met protein (UniProt.org). M118L has been identified in the scientific literature (PMID: 26700204), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D1228A missense unknown MET D1228A lies within the protein kinase domain of the Met protein (UniProt.org). D1228A is associated with resistance to some Met inhibitors in the context of TPR-MET (PMID: 21697284), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Jul 2018). Y
H1112L missense gain of function MET H1112L (corresponds to H1094L in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). H1112L confers a gain of function to Met, resulting in increased Met phosphorylation and activation of downstream signaling, and is transforming in cell culture (PMID: 19783361, PMID: 24061647).
H644N missense unknown MET H644N lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). H644N has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
A354D missense no effect - predicted MET A354D lies within the Sema domain of the Met protein (UniProt.org). A354D has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
H1112Y missense gain of function MET H1112Y (corresponds to H1094Y in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). H1112Y confers a gain of function to Met, resulting in constitutive Met phosphorylation and activation of downstream signaling, and is transforming in cell culture (PMID: 15064724, PMID: 24061647).
C98F missense unknown MET C98F lies within the Sema domain of the Met protein (UniProt.org). C98F has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
Y205C missense no effect - predicted MET Y205C lies within the Sema domain of the Met protein (UniProt.org). Y205C has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
T698A missense unknown MET T698A lies within the IPT/TIG domain 2 of the Met protein (UniProt.org). T698A has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
F192L missense unknown MET F192L lies within the Sema domain of the Met protein (UniProt.org). F192L has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
P351A missense no effect - predicted MET P351A lies within the Sema domain of the Met protein (UniProt.org). P351A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
K305E missense unknown MET K305E lies within the Sema domain of the Met protein (UniProt.org). K305E has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
L342I missense unknown MET L342I lies within the Sema domain of the Met protein (UniProt.org). L342I has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
E994K missense unknown MET E994K does not lie within any known functional domains of the Met protein (UniProt.org). E994K has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
I367V missense no effect - predicted MET I367V lies within the Sema domain of the Met protein (UniProt.org). I367V has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
M1131T missense gain of function - predicted MET M1131T lies within the protein kinase domain of the Met protein (UniProt.org). M1131T, which corresponds to the predicted gain of function variant M1149T in isoform 2, results in constitutive Met autophosphorylation, but demonstrates substrate phosphorylation and transforming activity similar to wild-type Met in cell culture (PMID: 9826708).
M1268T missense gain of function MET M1268T (corresponds to M1250T in the canonical isoform) lies within the protein kinase domain and RANBP9-interacting region of the Met protein (UniProt.org). M1268T results in constitutive phosphorylation of Met and activation of Src, and is transforming in cell culture (PMID: 10871851).
E168K missense unknown MET E168K lies within the Sema domain of the Met protein (UniProt.org). E168K has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
exon14 unknown unknown MET exon 14 indicates an unspecified mutation has occurred in exon 14 of the MET gene.
N38K missense unknown MET N38K lies within the Sema domain of the Met protein (UniProt.org). N38K has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R1184Q missense gain of function - predicted MET R1184Q (corresponds to R1166Q in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). R1184Q has not been biochemically characterized, but results in increased cell proliferation and viability levels as compared to wild-type Met (PMID: 29533785).
L1333V missense unknown MET L1333V lies within the protein kinase domain of the Met protein (UniProt.org). L1333V has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
S441C missense unknown MET S441C lies within the Sema domain of the Met protein (UniProt.org). S441C has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
Q558* nonsense loss of function - predicted MET Q558* results in a premature truncation of the Met protein at amino acid 558 of 1390 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), Q558* is predicted to lead to a loss of Met protein function.
R1327C missense unknown MET R1327C lies within the protein kinase domain of the Met protein (UniProt.org). R1327C has not been characterized in the scientific literature and therefore, its effect on protein function is unknown (PubMed, Aug 2018).
R412G missense unknown MET R412G lies within the Sema domain of the Met protein (UniProt.org). R412G has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V1110I missense gain of function MET V1110I (corresponds to V1092I in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). V1110I confers a gain of function to Met, resulting in constitutive Met phosphorylation and is transforming in cell culture (PMID: 19783361).
I333L missense unknown MET I333L lies within the Sema domain of the Met protein (UniProt.org). I333L has been identified in sequencing studies (PMID: 24755471, PMID: 18186519), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
mutant unknown unknown MET mutant indicates an unspecified mutation in the MET gene.
N315S missense unknown MET N315S lies within the Sema domain of the Met protein (UniProt.org). N315S has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V504L missense unknown MET V504L lies within the Sema domain of the Met protein (UniProt.org). V504L has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
E25D missense unknown MET E25D does not lie within any known functional domains of the Met protein (UniProt.org). E25D has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R21M missense unknown MET R21M lies within the signal peptide of the Met protein (UniProt.org). R21M has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
F346L missense unknown MET F346L lies within the Sema domain of the Met protein (UniProt.org). F346L has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
T1010I missense unknown MET T1010I (corresponds to T992I in the canonical isoform) lies within the cytoplasmic domain of the Met protein (UniProt.org). The functional effect of T1010I is conflicting, as it has been reported both to have phosphorylation level and transforming capacity similar to wild-type Met protein (PMID: 20670955), and increased Met transforming capability and cell migration in culture (PMID: 14559814).
T50K missense no effect - predicted MET T50K lies within the Sema domain of the Met protein (UniProt.org). T50K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
T660R missense unknown MET T660R lies within the IPT/TIG domain 2 of the Met protein (UniProt.org). T660R has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R266S missense unknown MET R266S lies within the Sema domain of the Met protein (UniProt.org). R266S has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
N257T missense unknown MET N257T lies within the Sema domain of the Met protein (UniProt.org). N257T has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R1166Q missense unknown MET R1166Q lies within the protein kinase domain of the Met protein (UniProt.org). R1166Q has been identified in the scientific literature (PMID: 16189274, PMID: 25453846), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
A320V missense unknown MET A320V lies within the Sema domain of the Met protein (UniProt.org). A320V has been identified in the scientific literature (PMID: 25589003, PMID: 9140397), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
L1195V missense gain of function MET L1195V lies within the protein kinase domain of the Met protein (UniProt.org). L1195V results in increased substrate phosphorylation and is transforming in cell culture (PMID: 9826708).
D543N missense unknown MET D543N lies within the extracellular domain of the Met protein (UniProt.org). D543N has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
Y1230C missense gain of function MET Y1230C lies within the protein kinase domain of the Met protein (UniProt.org). Y1230C results in constitutive Met autophosphorylation and increased substrate phosphorylation, and is transforming in cell culture (PMID: 9826708) and confers confers resistance to crizotinib (PMID: 27666659). Y
F634L missense unknown MET F634L lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). F634L has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
M630V missense unknown MET M630V lies within the IPT/TIG 1 domain of the Met protein (UniProt.org). M630V has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
L1140F missense unknown MET L1140F lies within the protein kinase domain of the Met protein (UniProt.org). L1140F has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
W911* nonsense loss of function - predicted MET W911* results in a premature truncation of the Met protein at amino acid 911 of 1390 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W911* is predicted to lead to a loss of function.
dec exp none no effect MET dec exp indicates decreased expression of the Met protein. However, the mechanism causing the decreased expression is unspecified.
F228C missense unknown MET F228C lies within the Sema domain of the Met protein (UniProt.org). F228C has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
K303N missense unknown MET K303N lies within the Sema domain of the Met protein (UniProt.org). K303N has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
Y666C missense unknown MET Y666C lies within the IPT/TIG 2 domain 2 of the Met protein (UniProt.org). Y666C has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
F634S missense unknown MET F634S lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). F634S has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
N375S missense loss of function - predicted MET N375S lies within the extracellular Sema ligand-binding domain of the Met protein (UniProt.org). N375S is predicted to confer a loss of function to the Met protein, as demonstrated by decreased Met binding affinity for Hgf in cell culture (PMID: 19723643).
R547* nonsense loss of function - predicted MET R547* results in a premature truncation of the Met protein at amino acid 547 of 1390 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), R547* is predicted to lead to a loss of Met protein function.
V1220I missense unknown MET V1220I lies within the protein kinase domain of the Met protein (UniProt.org). V1220I results in increased Met phosphorylation, however, does not alter substrate phosphorylation or demonstrate transforming activity in cell culture (PMID: 9826708).
V37A missense unknown MET V37A lies within the Sema domain of the Met protein (UniProt.org). V37A has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R1022* nonsense loss of function - predicted MET R1022* results in a premature truncation of the Met protein at amino acid 1022 of 1390 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R1022* is predicted to lead to a loss of Met protein function.
Y1230H missense gain of function MET Y1230H lies within the protein kinase domain of the Met protein (UniProt.org). Y1230H results in constitutive Met autophosphorylation and increased substrate phosphorylation, and is transforming in cell culture (PMID: 9826708), and has been associated with acquired resistance to Xalkori (crizotinib) (PMID: 28522754). Y
P742A missense unknown MET P742A lies within the IPT/TIG domain 3 of the Met protein (UniProt.org). P742A has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
del exon14 deletion gain of function MET del exon14 is a Met splice variant caused by a mutation resulting in the deletion of exon 14 (PMID: 16397241). Del exon14 results in both increased Met protein stability and ligand-dependent downstream signaling (PMID: 25971938).
positive unknown unknown MET positive indicates the presence of the MET gene, mRNA, and/or protein.
A564T missense unknown MET A564T lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). A564T has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
T698S missense unknown MET T698S lies within the IPT/TIG domain 2 of the Met protein (UniProt.org). T698S has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
F63V missense unknown MET F63V lies within the Sema domain of the Met protein (UniProt.org). F63V has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
S33F missense unknown MET S33F lies within the Sema domain of the Met protein (UniProt.org). S33F has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D1228H missense gain of function MET D1228H (corresponding to D1246H in isoform 2) lies within the protein kinase domain of the Met protein (UniProt.org). D1228H results in constitutive Met autophosphorylation and increased substrate phosphorylation, and is transforming in cell culture (PMID: 9826708).
D1231Y missense unknown MET D1231Y lies within the protein kinase domain of the Met protein (UniProt.org). D1231Y has been identified as a putative Met inhibitor resistance mutation (PMID: 29128427), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Jul 2018). Y
A48V missense unknown MET A48V lies within the Sema domain of the Met protein (UniProt.org). A48V has been identified in sequencing studies (PMID: 22037554), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D1228V missense unknown MET D1228V lies within the protein kinase domain of the Met protein (UniProt.org). D1228V has been described as a secondary drug resistance mutation due to its inability to bind some Met inhibitors (PMID: 27694386), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Jul 2018). Y
R469Q missense unknown MET R469Q lies within the Sema domain of the Met protein (UniProt.org). R469Q has been identified in sequencing studies (PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
I638L missense unknown MET I638L lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). I638L has been identified in sequencing studies (PMID: 23033341), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
fusion unknown unknown MET fusion indicates a fusion of the MET gene, but the fusion partner is unknown.
P742L missense unknown MET P742L lies within the IPT/TIG domain 3 of the Met protein (UniProt.org). P742L has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
K2N missense unknown MET K2N lies within the extracellular domain of the Met protein (UniProt.org). K2N has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R1104K missense no effect - predicted MET R1104K (corresponds to R1086K in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). R1104K has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
H979Y missense no effect - predicted MET H979Y does not lie within any known functional domains of the Met protein (UniProt.org). H979Y has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
E221G missense unknown MET E221G lies within the Sema domain of the Met protein (UniProt.org). E221G has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
P485L missense unknown MET P485L lies within the Sema domain of the Met protein (UniProt.org). P485L has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
M1149T missense gain of function - predicted MET M1149T (corresponds to M1131T in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). M1149T results in constitutive Met autophosphorylation and promotes tumor formation in animal models, but is not transforming in cell culture (PMID: 9326629).
G225D missense unknown MET G225D lies within the Sema domain of the Met protein (UniProt.org). G225D has been identified in sequencing studies (PMID: 24140581), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
I639L missense unknown MET I639L lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). I639L has been identified in the scientific literature (PMID: 26536169), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
H1124D missense gain of function MET H1124D (corresponds to H1106D in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). H1124D results in weak activation of Met, leading to increased Met phosphorylation and transformation of cultured cells (PMID: 10327054).
S525T missense unknown MET S525T lies within the extracellular domain of the Met protein (UniProt.org). S525T has been identified in sequencing studies (PMID: 22722839), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D824Y missense unknown MET D824Y lies within the IPT/TIG domain 3 of the Met protein (UniProt.org). D824Y has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
F1200L missense unknown MET F1200L lies within the protein kinase domain of the Met protein (UniProt.org). F1200L has been described as a secondary drug resistance mutation (PMID: 28765324), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Jul 2018). Y
G1163R missense unknown MET G1163R lies within the protein kinase domain of the Met protein (UniProt.org). G1163R has been described as a secondary drug resistance mutation due to its inability to bind some Met inhibitors (PMID: 21697284, PMID: 28765324), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Jul 2018). Y
K183N missense unknown MET K183N lies within the Sema domain of the Met protein (UniProt.org). K183N has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V136I missense unknown MET V136I lies within the Sema domain of the Met protein (UniProt.org). V136I has been identified in the scientific literature (PMID: 18709663, PMID: 21970370), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
A1251T missense unknown MET A1251T lies within the protein kinase domain of the Met protein (UniProt.org). A1251T has been identified in sequencing studies (PMID: 26373574), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D1117G missense unknown MET D1117G lies within the protein kinase domain of the Met protein (UniProt.org). D1117G has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
M1250T missense gain of function MET M1250T lies within the protein kinase domain of the Met protein (UniProt.org). M1250T confers a gain of function to the Met protein as demonstrated by transformation in culture, increased Met kinase activity (PMID: 28061464), and activation of the Ras signaling pathway (PMID: 11571647).
D1246H missense gain of function MET D1246H (corresponds to D1228H in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). D1246H results in constitutive Met autophosphorylation, is transforming in cell culture, and promotes tumor formation in animal models (PMID: 9326629).
R547Q missense unknown MET R547Q lies within the extracellular domain of the Met protein (UniProt.org). R547Q has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V378I missense unknown MET V378I lies within the Sema domain of the Met protein (UniProt.org). V378I has been identified in the scientific literature (PMID: 26887047), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
F434C missense no effect - predicted MET F434C lies within the Sema domain of the Met protein (UniProt.org). F434C has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
D1180Y missense unknown MET D1180Y lies within the protein kinase domain of the Met protein (UniProt.org). D1180Y has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
P712R missense unknown MET P712R lies within the IPT/TIG 2 domain of the Met protein (UniProt.org). P712R has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
I639V missense unknown MET I639V lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). I639V has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
negative unknown loss of function MET negative indicates a lack of the MET gene, mRNA, and/or protein.
M357V missense unknown MET M357V lies within the Sema domain of the Met protein (UniProt.org). M357V has been identified in sequencing studies (PMID: 26168399 ), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D414N missense unknown MET D414N lies within the Sema domain of the Met protein (UniProt.org). D414N has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
H476Y missense unknown MET H476Y lies within the Sema domain of the Met protein (UniProt.org). H476Y has been identified in sequencing studies (PMID: 25303977), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
wild-type none no effect Wild-type MET indicates that no mutation has been detected within the MET gene.
over exp none no effect MET over exp indicates an over expression of the Met protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
W540S missense unknown MET W540S lies within the extracellular domain of the Met protein (UniProt.org). W540S has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
T263M missense unknown MET T263M lies within the Sema domain of the Met protein (UniProt.org). T263M has been identified in sequencing studies (PMID: 22722193, PMID: 26214590, PMID: 25266736), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
L1213V missense gain of function MET L1213V (corresponds to L1195V in the canonical isoform) lies within the protein kinase domain and RANBP9-interacting region of the Met protein (UniProt.org). L1213V confers a gain of function to Met, resulting in constitutive Met phosphorylation and transformation of cultured cells (PMID: 15064724, PMID: 24061647).
L429V missense unknown MET L429V lies within the Sema domain of the Met protein (UniProt.org). L429V has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D1228N missense gain of function MET D1228N lies within the protein kinase domain of the Met protein (UniProt.org). D1228N results in constitutive Met autophosphorylation and increased substrate phosphorylation, and is transforming in cell culture (PMID: 9826708), and has been associated with acquired resistance to Xalkori (crizotinib) (PMID: 28522754). Y
W540* nonsense loss of function - predicted MET W540* results in a premature truncation of the Met protein at amino acid N540 of 1390 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), W540* is predicted to lead to a loss of Met protein function.
R412C missense unknown MET R412C lies within the Sema domain of the Met protein (UniProt.org). R412C has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
N393K missense unknown MET N393K lies within the Sema domain of the Met protein (UniProt.org). N393K has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V237fs frameshift loss of function - predicted MET V237fs results in a change in the amino acid sequence of the Met protein beginning at aa 237 of 1390 likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), V237fs is predicted to lead to a loss of Met protein function.
F1200I missense gain of function - predicted MET F1200I (corresponding to F1218I in isoform 2) lies within the protein kinase domain of the Met protein (UniProt.org). F1200I results in increased Met phosphorylation in the context of TPR-MET in an in vitro assay, and is also associated with resistance to some Met inhibitors in the context of TPR-MET (PMID: 21697284). Y
V1155L missense unknown MET V1155L lies within the protein kinase domain of the Met protein (UniProt.org). V1155L is associated with resistance to some Met inhibitors in the context of TPR-MET (PMID: 21697284), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Jul 2018). Y
V1206L missense gain of function MET V1206L (corresponds to V1188L in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). V1206L confers a gain of function to Met, resulting in increased Met phosphorylation in cell culture (PMID: 19783361, PMID: 24061647).
I565M missense unknown MET I565M lies within the IPT/TIG domain 1 of the Met protein (UniProt.org). I565M has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
S203Y missense unknown MET S203Y lies within the Sema domain of the Met protein (UniProt.org). S203Y has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
G1144R missense unknown MET G1144R (also referred to as G1162R) lies within the protein kinase domain of the Met protein (UniProt.org). G1144R has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R1170* nonsense loss of function - predicted MET R1170* results in a premature truncation of the Met protein at amino acid 1170 of 1390 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R1170* is predicted to lead to a loss of Met protein function.
K306N missense unknown MET K306N lies within the Sema domain of the Met protein (UniProt.org). K306N has been identified in sequencing studies (PMID: 22722201), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
P1060S missense unknown MET P1060S lies within the cytoplasmic domain of the Met protein (UniProt.org). P1060S has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
D1010I missense unknown MET D1010I does not lie within any known functional domains of the Met protein (UniProt.org). D1010I has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
T733K missense unknown MET T733K lies within the IPT/TIG domain 2 of the Met protein (UniProt.org). T733K has been identified in sequencing studies (PMID: 23917401), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
E168D missense unknown MET E168D lies within the Sema domain of the Met protein (UniProt.org). The functional effect of E168D is conflicting as E168D resulted in an increased affinity of Met for Hgf in an in vitro assay (PMID: 19723643), but decreased cell proliferation and cell viability as compared to wild-type Met in another study (PMID: 29533785).
M362T missense unknown MET M362T lies within the extracellular Sema ligand-binding domain of the Met protein (UniProt.org). M362T has been identified in the scientific literature (PMID: 27438523), but has not been biochemically characterized and therefore, its effect on protein function is unknown (PubMed, Aug 2018).
R988C missense gain of function MET R988C (corresponds to R970C in the canonical isoform) lies within the juxtamembrane domain of the Met protein (PMID: 14559814, UniProt.org). R988C does not increase Met phosphorylation, but results in increased phosphorylation of cellular proteins, and increased proliferation and migration of cultured cells (PMID: 14559814, PMID: 20670955, PMID: 22973954).
Y1230S missense unknown MET Y1230S lies within the protein kinase domain of the Met protein (UniProt.org). Y1230S has been associated with acquired resistance to Xalkori (crizotinib) (PMID: 28522754), but has not been characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018). Y
Y1235D missense gain of function MET Y1235D (also referred to as Y1253D) lies in a phosphorylation site within the protein kinase domain of the Met protein (UniProt.org). Y1235D (Y1253D) results in increased Met kinase activity in in vitro assays (PMID: 16245927, PMID: 19459657).
P97L missense unknown MET P97L lies within the Sema domain of the Met protein (UniProt.org). P97L has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
S717* nonsense loss of function - predicted MET S717* results in a premature truncation of the Met protein at amino acid 717 of 1390 (UniProt.org). Due to the loss of several functional domains, including the protein kinase domain (UniProt.org), S717* is predicted to lead to a loss of Met protein function.
Y1248H missense gain of function MET Y1248H (corresponds to Y1230H in the canonical isoform) lies within the protein kinase domain and RANBP9-interacting region of the Met protein (UniProt.org). Y1248H results in constitutive Met phosphorylation, is transforming in cell culture, and promotes tumor formation in mice (PMID: 15064724, PMID: 9326629).
E1253K missense unknown MET E1253K lies within the protein kinase domain of the Met protein (UniProt.org). E1253K has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V1238I missense gain of function MET V1238I (corresponds to V1220I) lies within the protein kinase domain and RANBP9-interacting region of the Met protein (UniProt.org). V1238I confers a gain of function to Met, resulting in increased Met phosphorylation in cell culture and promotes tumor formation in mice (PMID: 19783361, PMID: 9326629).
S213L missense unknown MET S213L lies within the Sema domain of the Met protein (UniProt.org). S213L has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
V1188L missense no effect MET V1188L lies within the protein kinase domain of the Met protein (UniProt.org). V1188L demonstrates substrate phosphorylation and transforming activity similar to wild-type Met in cell culture (PMID: 9826708).
L964M missense unknown MET L964M lies within the cytoplasmic domain of the Met protein (UniProt.org). L964M has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
H1112R missense gain of function - predicted MET H1112R (corresponds to H1094R in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). H1112R has not been characterized with respect to Met protein function; however, H1112R leads to transformation of cells in culture, thus is predicted to result in a gain of function (PMID: 9563489).
L238F missense unknown MET L238F lies within the Sema domain of the Met protein (UniProt.org). L238F has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
S135N missense unknown MET S135N lies within the Sema domain of the Met protein (UniProt.org). S135N has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
G1163T missense unknown MET G1163T (corresponding to G1182T in isoform 2) lies within the protein kinase domain of the Met protein (UniProt.org). G1163T has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
N1118Y missense gain of function MET N1118Y (corresponds to N1100Y in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). N1118Y results in increased Met kinase activity, increased cell proliferation and invasive phenotype in cultured cells (PMID: 12460923).
V427G missense unknown MET V427G lies within the Sema domain of the Met protein (UniProt.org). V427G has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
R413G missense no effect - predicted MET R413G lies within the Sema domain of the Met protein (UniProt.org). R413G has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
V486A missense no effect - predicted MET V486A lies within the Sema domain of the Met protein (UniProt.org). V486A has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
L296P missense unknown MET L296P lies within the Sema domain of the Met protein (UniProt.org). L296P has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
M1210I missense no effect - predicted MET M1210I (corresponds to M1192I in the canonical isoform) lies within the protein kinase domain of the Met protein (UniProt.org). M1210I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Met (PMID: 29533785).
S525Y missense unknown MET S525Y lies within the extracellular domain of the Met protein (UniProt.org). S525Y has not been characterized in the scientific literature and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
A887Sfs*3 frameshift loss of function - predicted MET A887Sfs*3 indicates a shift in the reading frame starting at amino acid 887 and terminating 3 residues downstream causing a premature truncation of the 1390 amino acid Met protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), A887Sfs*3 is predicted to result in a loss of Met protein function (PubMed, Aug 2018).
Y1003fs frameshift gain of function - predicted MET Y1003fs results in a change in the amino acid sequence of the Met protein beginning at aa 1003 of 1390, likely resulting in premature truncation of the functional protein (UniProt.org). Y1003fs has not been characterized, however, Y1003* results in exon 14 skipping and Met activation (PMID: 25531467, PMID: 16397241) and therefore, Y1003fs is predicted to result in a gain of function.
T474I missense unknown MET T474I lies within the Sema domain of the Met protein (UniProt.org). T474I has been identified in sequencing studies (PMID: 22722839), but has not been biochemically characterized and therefore, its effect on Met protein function is unknown (PubMed, Aug 2018).
amp none no effect MET amp indicates an increased number of copies of the MET gene. However, the mechanism causing the increase is unspecified.
act mut unknown gain of function MET act mut indicates that this variant results in a gain of function in the MET protein. However, the specific amino acid change has not been identified.
Molecular Profile Protein Effect Treatment Approaches
MET Y1003* gain of function MET Antibody MET Inhibitor
MET Y1230D gain of function MET Inhibitor
MET H644Y no effect - predicted
MET L707V unknown
MET R417* loss of function - predicted
MET E167K unknown
MET Y321H unknown
MET L238Yfs*25 loss of function - predicted
MET P295H unknown
MET T992I unknown
MET M118L unknown
MET D1228A unknown
MET H1112L gain of function MET Inhibitor
MET H644N unknown
MET A354D no effect - predicted
MET H1112Y gain of function MET Inhibitor
MET C98F unknown
MET Y205C no effect - predicted
MET T698A unknown
MET F192L unknown
MET P351A no effect - predicted
MET K305E unknown
MET L342I unknown
MET E994K unknown
MET I367V no effect - predicted
MET M1131T gain of function - predicted MET Inhibitor
MET M1268T gain of function MET Inhibitor
MET E168K unknown
MET exon 14 unknown
MET N38K unknown
MET R1184Q gain of function - predicted MET Inhibitor
MET L1333V unknown
MET S441C unknown
MET Q558* loss of function - predicted
MET R1327C unknown
MET R412G unknown
MET V1110I gain of function MET Inhibitor
MET I333L unknown
MET alterations
MET mutant unknown
MET N315S unknown
MET V504L unknown
MET E25D unknown
MET R21M unknown
MET F346L unknown
MET T1010I unknown MET Inhibitor
MET T50K no effect - predicted
MET T660R unknown
MET R266S unknown
MET N257T unknown
MET R1166Q unknown
MET A320V unknown
MET L1195V gain of function MET Inhibitor
MET amp MET del exon14 MET D1228N MET G1163R MET L1195V
MET D543N unknown
MET del exon14 MET Y1230C
MET over exp MET Y1230C MET Y1230H
MET Y1230C gain of function MET Inhibitor
MET over exp MET Y1230C
MET F634L unknown
MET M630V unknown
MET L1140F unknown
MET W911* loss of function - predicted
MET dec exp no effect
FGFR1 amp MET dec exp
BRCA2 dec exp MET dec exp
BRCA1 dec exp MET dec exp
MET F228C unknown
MET K303N unknown
MET Y666C unknown
MET F634S unknown
MET N375S loss of function - predicted
ERBB2 pos KRAS amp MET N375S
MET R547* loss of function - predicted
MET V1220I unknown
MET V37A unknown
MET R1022* loss of function - predicted
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S
MET over exp MET Y1230H
MET F1200L MET Y1230H
MET Y1230H gain of function MET Inhibitor
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H
MET P742A unknown
MET del exon14 MET D1228N
CDKN2A mut MET del exon14 PDGFRA mut SMAD4 Q249H
MET del exon14 TP53 N30fs
MET del exon14 TP53 R175H
MET amp MET del exon14
MET del exon14 gain of function MET Antibody MET Inhibitor
FGFR1 amp MET pos
MET positive unknown
ERBB2 neg MET pos
MET A564T unknown
MET T698S unknown
MET F63V unknown
MET S33F unknown
MET D1228H gain of function MET Inhibitor
EGFR L858R EGFR T790M MET amp MET D1231Y
MET D1231Y unknown
MET A48V unknown
MET D1228V unknown
EGFR exon 19 del MET amp MET D1228V
MET R469Q unknown
MET I638L unknown
MET fusion unknown
MET P742L unknown
MET K2N unknown
MET R1104K no effect - predicted
MET H979Y no effect - predicted
MET E221G unknown
MET P485L unknown
MET M1149T gain of function - predicted MET Inhibitor
MET G225D unknown
MET I639L unknown
MET H1124D gain of function MET Inhibitor
MET S525T unknown
MET D824Y unknown
MET F1200L unknown
MET G1163R unknown
MET K183N unknown
MET V136I unknown
MET A1251T unknown
MET D1117G unknown
MET M1250T gain of function MET Inhibitor
MET D1246H gain of function MET Inhibitor
MET R547Q unknown
MET V378I unknown
MET F434C no effect - predicted
MET D1180Y unknown
MET P712R unknown
MET I639V unknown
MET negative loss of function
MET M357V unknown
MET D414N unknown
MET H476Y unknown
MET wild-type no effect
EGFR wild-type MET wild-type
KRAS G12D MET over exp
FGFR1 amp MET over exp
MET over exp no effect HGF Antibody MET Antibody MET Inhibitor
EGFR wild-type MET over exp
BRCA1 dec exp MET over exp
BRAF D594N BRAF G466A EGFR over exp MET over exp
BRCA2 dec exp MET over exp
MET amp over exp
MET over exp TP53 dec exp
MET W540S unknown
MET T263M unknown
MET L1213V gain of function MET Inhibitor
MET L429V unknown
MET D1228N gain of function MET Inhibitor
MET W540* loss of function - predicted
MET R412C unknown
MET N393K unknown
MET V237fs loss of function - predicted
MET F1200I gain of function - predicted MET Inhibitor
MET V1155L unknown
MET V1206L gain of function MET Inhibitor
MET I565M unknown
MET S203Y unknown
MET G1144R unknown
MET R1170* loss of function - predicted
MET K306N unknown
MET P1060S unknown
MET D1010I unknown
MET T733K unknown
MET E168D unknown MET Inhibitor
MET M362T unknown
ERBB2 over exp MET amp MET R988C
KIT S476I MET R988C
MET R988C gain of function MET Inhibitor
MET Y1230S unknown
MET Y1235D gain of function MET Inhibitor
MET P97L unknown
MET S717* loss of function - predicted
MET Y1248H gain of function MET Inhibitor
MET E1253K unknown
MET V1238I gain of function MET Inhibitor
MET S213L unknown
MET V1188L no effect
MET L964M unknown
MET H1112R gain of function - predicted MET Inhibitor
MET L238F unknown
MET S135N unknown
MET G1163T unknown
MET N1118Y gain of function MET Inhibitor
MET V427G unknown
MET R413G no effect - predicted
MET V486A no effect - predicted
MET L296P unknown
MET M1210I no effect - predicted
MET S525Y unknown
MET A887Sfs*3 loss of function - predicted
MET Y1003fs gain of function - predicted MET Antibody MET Inhibitor
MET T474I unknown
ERBB2 over exp MET amp
KRAS G12D MET amp
EGFR exon 19 del MET amp
ERBB2 pos MET amp
BRAF V600E EGFR exon 19 del MET amp
KRAS G12V MET amp
EGFR L858R MET amp
EGFR exon 19 del EGFR T790M MET amp
EGFR act mut MET amp
ALK rearrange MET amp
FGFR1 amp MET amp
MET amp TP53 del
EGFR amp MET amp
EGFR T790M MET amp
MET amp no effect HGF Antibody MET Antibody MET Inhibitor
KRAS G12A MET amp
EGFR mut MET amp
ERBB2 amp MET amp
EGFR L858R EGFR T790M MET amp
EGFR E746_A750del MET amp
MET act mut gain of function MET Inhibitor
EGFR exon 19 del MET act mut
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET Y1230D Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET Y1230D in an in vitro kinase assay (PMID: 26285778). 26285778
MET H1112L cancer sensitive SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET H1112L demonstrated sensitivity to SU11274 treatment (PMID: 19783361). 19783361
MET H1112Y cancer sensitive SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET H1112Y demonstrated sensitivity to SU11274 treatment (PMID: 19783361). 15064724
MET M1268T cancer sensitive SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET M1268T demonstrated sensitivity to SU11274 treatment (PMID: 15064724). 15064724
MET M1268T cancer sensitive K252a Preclinical Actionable In preclinical studies, cell lines transformed by MET M1268T were sensitive to K252a treatment in both culture and mouse model experiments (PMID: 12118367). 12118367
MET exon 14 non-small cell lung carcinoma sensitive Capmatinib Phase I Actionable In a Phase I trial, Capmatinib (INC280) treatment resulted in partial response in 100% (2/2) of non-small cell lung carcinoma patients harboring MET exon 14 mutations (J Clin Oncol 34, 2016 (suppl; abstr 9067)). detail...
MET exon 14 non-small cell lung carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for non-small cell lung cancer patients with MET exon 14 mutations (NCCN.org). detail...
MET exon 14 non-small cell lung carcinoma predicted - sensitive Tepotinib Phase II Actionable In a Phase II trial, Tepotinib (MSC2156119J) treatment resulted in partial response in 60.0% (9/15) and stable disease in 20% (3/15) of patients with non-small cell lung cancer harboring MET exon 14 skipping mutations (J Clin Oncol 36, 2018 (suppl; abstr 9016); NCT02864992). detail...
MET V1110I cancer sensitive SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET V1110I demonstrated sensitivity to SU11274 treatment (PMID: 19783361). 19783361
MET T1010I lung carcinoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, lung carcinoma cell lines harboring MET T1010I showed sensitivity to Xalkori (crizotinib) in cell culture (PMID: 17483355). 17483355
MET amp MET del exon14 MET D1228N MET G1163R MET L1195V lung adenocarcinoma resistant Glesatinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient previously harboring MET amp, MET deletion exon 14, MET D1228N, MET Y1230H, MET Y1230S, and MET G1163R demonstrated a decrease in lesion size when treated with Glesatinib (MGCD265), however, progression ensued and plasma testing indicated the patient lost Y1230H and Y1230S, but acquired MET L1195V (PMID: 28765324). 28765324
MET del exon14 MET Y1230C Advanced Solid Tumor sensitive Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing MET deletion exon 14 and MET Y1230C were sensitive to Glesatinib (MGCD265) treatment, demonstrating cell growth inhibition in culture and 52% tumor regression in xenograft models (PMID: 28765324). 28765324
MET over exp MET Y1230C MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, acquired MET Y1230C and MET Y1230H mutations were associated with secondary resistance to Xalkori (crizotinib) in a MET-over expressing gastric cancer cell line xenograft model, and cells derived from this model demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21266357). 21266357
MET Y1230C Advanced Solid Tumor sensitive Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, a transformed cell line expressing MET Y1230C was sensitive to Glesatinib (MGCD265), demonstrating inhibition of cell growth in culture and 88% tumor regression in xenograft models (PMID: 28765324). 28765324
MET Y1230C stomach cancer resistant Capmatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) treated with Capmatinib (INC280) in culture for several months developed resistance and was found to harbor MET Y1230C (PMID: 28765324). 15494073 28765324
MET Y1230C Advanced Solid Tumor sensitive Merestinib Preclinical - Cell culture Actionable In a preclinical study, Merestinib (LY2801653) inhibited growth of transformed cells over expressing MET Y1230C in culture (PMID: 23275061). 23275061
MET Y1230C Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET Y1230C in an in vitro kinase assay (PMID: 26285778). 26285778
MET Y1230C stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a Capmatinib (INC280)-resistant gastric cancer cell line (PMID: 15494073) harboring MET Y1230C also demonstrated resistance when treated with Xalkori (crizotinib) (PMID: 28765324). 15494073 28765324
MET Y1230C stomach cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) harboring MET Y1230C was sensitive to treatment with Glesatinib (MGCD265), demonstrating cell growth inhibition in culture (PMID: 28765324). 28765324 15494073
MET over exp MET Y1230C stomach cancer resistant PHA-665752 Preclinical - Cell line xenograft Actionable In a preclinical study, an acquired MET Y1230C mutation was associated with resistance to PHA-665752 in a MET-over expressing gastric cancer cell line xenograft model, and cells derived from this xenograft model demonstrated sustained MET activation following treatment with PHA-665752 in culture (PMID: 21266357). 21266357
MET dec exp triple-receptor negative breast cancer sensitive Olaparib Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cell lines with decreased Met expression via shRNA knockdown demonstrated increased sensitivity to Lynparza (olaparib) induced growth and colony formation inhibition in culture (PMID: 26779812). 26779812
MET dec exp triple-receptor negative breast cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, triple-receptor negative breast cancer cell lines with decreased Met expression via shRNA knockdown demonstrated increased sensitivity to Rubraca (rucaparib) induced growth and colony formation inhibition in culture (PMID: 26779812). 26779812
MET dec exp triple-receptor negative breast cancer sensitive Veliparib Preclinical - Cell culture Actionable In a preclinical study, triple-receptor negative breast cancer cell lines with decreased Met expression via shRNA knockdown demonstrated increased sensitivity to Veliparib (ABT-888) induced growth and colony formation inhibition in culture (PMID: 26779812). 26779812
FGFR1 amp MET dec exp lung cancer sensitive Rogaratinib Preclinical - Cell culture Actionable In a preclinical study, Rogaratinib (BAY 1163877) inhibited Erk signaling and proliferation of FGFR1-amplified lung cancer cell lines with undetectable Met expression in culture (PMID: 27429073). 27429073
FGFR1 amp MET dec exp lung cancer sensitive AZD4547 Preclinical - Cell culture Actionable In a preclinical study, AZD4547 inhibited Erk signaling and proliferation of FGFR1-amplified lung cancer cell lines with undetectable Met expression in culture (PMID: 27429073). 27429073
BRCA2 dec exp MET dec exp triple-receptor negative breast cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca2 expression via shRNA knockdown sensitized triple-receptor negative breast cancer cells with low expression of Met to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
BRCA1 dec exp MET dec exp triple-receptor negative breast cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca1 expression via shRNA knockdown sensitized triple-receptor negative breast cancer cells with low expression of Met to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
MET N375S oral cavity cancer no benefit Crizotinib Clinical Study Actionable In a clinical case study, a patient with oral cavity cancer harboring MET N375S demonstrated progressive disease and overall survival of five weeks when treated with Xalkori (crizotinib) (PMID: 28514312). 28514312
MET N375S Advanced Solid Tumor decreased response SU11274 Preclinical Actionable In a preclinical study, cells expressing MET N375S had decreased sensitivity to SU11274 in culture compared to cells expressing wild-type MET (PMID: 19723643). 19723643
MET N375S ovarian carcinoma sensitive Bevacizumab + Sorafenib Clinical Study Actionable In a clinical case study, a patient with ovarian cancer harboring MET N375S demonstrated sensitivity to the combination treatment, Nexavar (sorafenib) and Avastin (bevacizumab), resulting in stable disease for greater than six months (PMID: 25363205). 25363205
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S lung adenocarcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring MET deletion exon 14 responded to Xalkori (crizotinib), demonstrating a near complete response at 3 months, however, after 9 months progression ensued and a re-biospy identified MET del exon14, MET amplification, MET D1228N, MET Y1230H, MET Y1230S, and MET G1163R (PMID: 28522754). 28522754
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S lung adenocarcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring MET deletion exon 14 and MET amplification demonstrated resistance to Xalkori (crizotinib), and the patient was found to have acquired MET Y1230H, MET D1228N, MET Y1230S, and MET G1163R (PMID: 28765324). 28765324
MET over exp MET Y1230H stomach cancer resistant PHA-665752 Preclinical - Cell line xenograft Actionable In a preclinical study, MET Y1230H was associated with resistance to PHA-665752 in a gastric cancer cell line with MET over expression in culture (PMID: 21266357). 21266357
MET F1200L MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) treated with Xalkori (crizotinib) in culture for several months developed resistance and was found to co-harbor MET Y1230H and MET F1200L(PMID: 28765324). 28765324 15494073
MET F1200L MET Y1230H stomach cancer resistant Capmatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) co-harboring MET Y1230H and MET F1200L demonstrated resistance when treated with Capmatinib (INC280) in culture (PMID: 28765324). 28765324 15494073
MET F1200L MET Y1230H stomach cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) co-harboring MET Y1230H and MET F1200L was sensitive to treatment with Glesatinib (MGCD265), demonstrating cell growth inhibition in culture (PMID: 28765324). 28765324 15494073
MET Y1230H Advanced Solid Tumor predicted - resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Savolitinib (AZD6094), demonstrating sustained cell growth in culture (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Xalkori (crizotinib), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in cell line xenograft mouse models (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - sensitive BMS-777607 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to Y1230H in humans) were sensitive to treatment with BMS-777607 (ASLAN002), demonstrating inhibition of cell growth in culture (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - sensitive Cabozantinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were sensitive to treatment with Cometriq (Cabometyx, cabozantinib), demonstrating inhibition of cell growth in culture and tumor growth inhibition in mouse models (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET Y1230H in an in vitro kinase assay (PMID: 26285778). 26285778
MET Y1230H Advanced Solid Tumor predicted - resistant Capmatinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Capmatinib (INC280), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in mouse models (PMID: 28396313). 28396313
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H lung adenocarcinoma predicted - resistant Crizotinib + Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR T790M and MET amplification demonstrated progressive disease after 3 months of treatment with the combination of Tagrisso (osimertinib) and Xalkori (crizotinib) and was found to have acquired 4 MET mutations: MET D1228H, MET D1228N, MET Y1230H, and MET D1231Y (PMID: 29128427). 29128427
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H lung adenocarcinoma unknown Cabozantinib + Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR T790M, MET amplification and MET D1228H, MET D1228N, MET Y1230H, and MET D1231Y demonstrated initial symptomatic improvement, decreased pleural effusion, and lung nodule shrinkage following treatment with the combination of Cometriq (Cabometyx, cabozantinib) and Tagrisso (osimertinib) (PMID: 29128427). 29128427
MET del exon14 MET D1228N lung squamous cell carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with squamous cell lung cancer harboring a MET exon 14 skipping mutation was determined to have acquired MET D1228N after progression on Xalkori (crizotinib) therapy (PMID: 27343442). 27343442
MET del exon14 MET D1228N Advanced Solid Tumor sensitive Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing MET deletion exon 14 and MET D1228N were sensitive to Glesatinib (MGCD265) treatment, demonstrating cell growth inhibition in culture and 21% tumor regression in xenograft models (PMID: 28765324). 28765324
CDKN2A mut MET del exon14 PDGFRA mut SMAD4 Q249H melanoma sensitive Imatinib + Carboplatin + Paclitaxel Clinical Study Actionable In a clinical study, a melanoma patient harboring a PDGFRA mutation, CDKN2A mutation, MET exon 14 splice site mutation, and SMAD4 Q249H demonstrated a 21 month overall survival when treated with a combination of Gleevec (imatinib), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28514312). 28514312
MET del exon14 TP53 N30fs lung large cell carcinoma sensitive Capmatinib Clinical Study Actionable In a clinical case study, Capmatinib (INC280) treatment resulted in decreased tumor volume by 53% in a patient with large cell lung carcinoma harboring MET deletion exon 14 and TP53 N30fs*14 (PMID: 25971938). 25971938
MET del exon14 TP53 R175H histiocytic and dendritic cell cancer sensitive Crizotinib Clinical Study Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a decrease in tumor volume by more than 60% in a patient with histiocytic sarcoma harboring MET deletion exon 14 and TP53 R175H (PMID: 25971938). 25971938
MET amp MET del exon14 lung adenocarcinoma sensitive Crizotinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient co-harboring MET exon 14 deletion and MET amp was sensitive to Xalkori (crizotinib), demonstrating a partial response for 8 months (PMID: 28765324). 28765324
MET amp MET del exon14 non-small cell lung carcinoma sensitive SCC244 Preclinical - Pdx Actionable In a preclinical study, non-small cell lung carcinoma patient derived xenograft (PDX) models co-harboring MET amplification and MET deletion of exon 14 were sensitive to SCC244 treatment, demonstrating a complete response in four and a partial response in another four (PMID: 29237805). 29237805
MET amp MET del exon14 lung cancer sensitive Glesatinib Preclinical - Pdx Actionable In a preclinical study, a lung cancer patient-derived xenograft (PDX) model harboring MET amplification and MET exon 14 deletion demonstrated tumor regression when treated with Glesatinib (MGCD265) (PMID: 28765324). 28765324
MET amp MET del exon14 non-small cell lung carcinoma sensitive Glesatinib Preclinical - Pdx Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in tumor regression in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring deletion of MET exon 14 and varying degrees of MET amplification (PMID: 28765324). 28765324
MET del exon14 lung adenocarcinoma sensitive Crizotinib Clinical Study Actionable In a clinical case study, three patients with lung adenocarcinoma harboring a deletion of MET exon 14 demonstrated partial responses when treated with Xalkori (crizotinib) (PMID: 25971939). 25971939
MET del exon14 non-small cell lung carcinoma sensitive KTN0073-IgG1 Preclinical - Cell culture Actionable In a preclinical study, KTN0073-IgG1 inhibited growth of a non-small cell lung cancer cell line harboring deletion of MET exon 14 in culture (PMID: 27550450). 27550450
MET del exon14 lung adenocarcinoma sensitive Glesatinib Clinical Study Actionable In a clinical study, a patient with lung adenocarcinoma harboring a deletion of MET exon 14 demonstrated a 66% reduction in target lesion size and maintained a partial response for 7 months when treated with Glesatinib (MGCD265) (PMID: 28765324). 28765324
MET del exon14 Advanced Solid Tumor sensitive SYM015 Preclinical - Pdx & cell culture Actionable In a preclinical study, Sym015 inhibited growth of cancer cell lines harboring MET exon 14 deletion in culture, and inhibited tumor growth in patient-derived xenograft (PDX) models with MET exon 14 deletion (Cancer Res July 15 2016 (76) (14 Supplement) 1219). detail...
MET del exon14 lung squamous cell carcinoma sensitive Capmatinib Clinical Study Actionable In a clinical case study, Capmatinib (INC280) treatment resulted in a decreased tumor volume of 61% in a patient with lung squamous cell carcinoma harboring a deletion of MET exon 14 (PMID: 25971938). 25971938
MET del exon14 Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing MET del exon14 were sensitive to Xalkori (crizotinib) treatment in culture, demonstrating inhibition of spheroid growth (PMID: 28765324). 28765324
MET del exon14 Advanced Solid Tumor sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing deletion of MET exon 14 were sensitive to Glesatinib (MGCD265) treatment in culture, demonstrating inhibition of spheroid growth (PMID: 28765324). 28765324
MET del exon14 non-small cell lung carcinoma sensitive Onartuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, Onartuzumab inhibited tumor growth and decreased MET expression in a non-small cell lung cancer xenograft model harboring MET exon 14 deletion (PMID: 23882082). 23882082
MET del exon14 stomach cancer sensitive Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) inhibited Met phosphorylation and growth in gastric cancer cells harboring MET exon 14 deletion and amplification of the mutant allele in culture, and resulted in tumor regression in cell line xenograft models (PMID: 28765324). 28765324
MET del exon14 lung adenocarcinoma sensitive Cabozantinib Clinical Study Actionable In a clinical study, a patient with lung adenocarcinoma harboring a deletion of MET exon 14 demonstrated a complete response via PERCIST criteria when treated with Cometriq (Cabometyx, cabozantinib) (PMID: 25971939). 25971939
MET del exon14 stomach cancer decreased response Emibetuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, Emibetuzumab (LY2875358) treatment resulted in initial tumor growth inhibition followed by regrowth in cell line xenograft models of gastric cancer harboring MET exon 14 skipping mutations (PMID: 28679766). 28679766
MET del exon14 lung cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, Glesatinib (MGCD265) inhibited Met phosphorylation and growth in lung cancer cells harboring MET exon 14 deletion and loss of the wild-type MET allele in culture (PMID: 28765324). 28765324
MET del exon14 lung cancer decreased response Emibetuzumab Preclinical - Pdx Actionable In a preclinical study, Emibetuzumab (LY2875358) treatment resulted in initial tumor growth inhibition followed by regrowth in patient-derived xenograft (PDX) models of lung cancer harboring MET exon 14 skipping mutations (PMID: 28679766). 28679766
MET del exon14 lung cancer sensitive SYM015 Preclinical - Pdx Actionable In a preclinical study, SYM015 treatment resulted in sustained tumor growth inhibition in patient-derived xenograft (PDX) models of lung cancer harboring MET exon 14 skipping (PMID: 28679766). 28679766
MET del exon14 stomach cancer sensitive SYM015 Preclinical - Cell line xenograft Actionable In a preclinical study, SYM015 treatment resulted in sustained tumor growth inhibition in cell line xenograft models of gastric cancer harboring MET exon 14 skipping (PMID: 28679766). 28679766
MET del exon14 Advanced Solid Tumor sensitive Capmatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing MET deletion exon 14 were sensitive to Capmatinib (INC280) treatment in culture, demonstrating inhibition of spheroid growth (PMID: 28765324). 28765324
FGFR1 amp MET pos lung cancer resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, FGFR1-amplified lung cancer cell lines with Met expression were resistant to AZD4547 in culture (PMID: 27429073). 27429073
FGFR1 amp MET pos lung cancer resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, FGFR1-amplified lung cancer cell lines with Met expression were resistant to Rogaratinib (BAY 1163877) in culture (PMID: 27429073). 27429073
MET positive non-small cell lung carcinoma sensitive Telisotuzumab vedotin Phase I Actionable In a Phase I clinical trial, ABBV-399 was well-tolerated and demonstrated preliminary efficacy in patients with MET-positive non-small cell lung cancer, with 30% (3/10) of patients demonstrating a partial response (J Clin Oncol 34, 2016 (suppl; abstr 2510)). detail...
MET positive glioblastoma multiforme sensitive Ningetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ningetinib inhibited Met phosphorylation in tumor tissue, resulted in prolonged median survival time and significantly increased life-span in cell line xenograft models of glioblastoma (Cancer Res 2014;74(19 Suppl):Abstract nr 1755). detail...
MET positive Advanced Solid Tumor no benefit AMG208 Phase I Actionable In a Phase I trial, Met expression and mutation status were not associated with response to AMG208 treatment in patients with advanced solid tumor (PMID: 26155941; NCT00813384). 26155941
MET positive non-small cell lung carcinoma sensitive Emibetuzumab + Erlotinib Phase I Actionable In a Phase I trial, Emibetuzumab (LY2875358) and Tarceva (erlotinib) combination treatment resulted in durable partial response in 14.3% (2/14) of patients with non-small cell lung carcinoma, with both responders being Met positive (PMID: 27803065). 27803065
MET positive non-small cell lung carcinoma sensitive Emibetuzumab + Erlotinib Phase I Actionable In a Phase I trial, Emibetuzumab (LY2875358) and Tarceva (erlotinib) combination treatment resulted in durable partial response in 15% (2/13) of Met-positive patients with non-small cell lung carcinoma (J Clin Oncol 31, 2013 (suppl; abstr 8093)). detail...
MET positive non-small cell lung carcinoma conflicting Onartuzumab + Erlotinib Phase III Actionable In a Phase II clinical trial, Onartuzumab (RO5490258), in combination with Tarceva (erlotinib) demonstrated efficacy in patients with Met-positive NSCLC (PMID: 24101053). However, a subsequent Phase III clinical trial has been unable to confirm this efficacy (J Clin Oncol 32:5s, 2014 (suppl; abstr 8000)). 24101053 detail...
MET positive glioblastoma multiforme predicted - sensitive Altiratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited viability of several MET-expressing glioblastoma cell lines in culture and inhibited tumor growth in cell line xenograft models (PMID: 26965451). 26965451
MET positive Advanced Solid Tumor sensitive Emibetuzumab Phase I Actionable In a Phase I trial, Emibetuzumab (LY2875358) treatment resulted in durable partial response in 4% (1/23) of Met-positive patients with advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 8093)). detail...
MET positive Advanced Solid Tumor predicted - sensitive Merestinib Preclinical - Pdx Actionable In a preclinical study, Merestinib (LY2801653) treatment resulted in growth inhibition correlating with Met expression level in a panel of patient-derived xenograft models of solid tumors (Cancer Res 2010;70(8 Suppl):Abstract nr 3611). detail...
MET positive clear cell sarcoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial (CREATE), Xalkori (crizotinib) treatment in MET-positive clear cell sarcoma patients resulted in an objective response rate of 3.8% (1/26) and a median progression-free survival of 131 days, similar to results achieved with first-line Adriamycin (doxorubicin) in non-selected metastatic soft tissue sarcomas (PMID: 28950372; NCT01524926). 28950372
MET positive non-small cell lung carcinoma sensitive Capmatinib Phase I Actionable In a Phase I trial, Capmatinib (INC280) treatment resulted in partial response in 19% (5/26) of MET-positive non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9067)). detail...
MET positive ovarian cancer predicted - sensitive Altiratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited MET activation, decreased viability and migration of c-MET positive ovarian cancer cells in culture, and reduced tumor growth in ovarian cancer cell line xenograft models (PMID: 24362531). 24362531
MET positive multiple myeloma predicted - sensitive Ficlatuzumab Phase I Actionable In a Phase I trial, Ficlatuzumab treatment resulted in stable disease in 57% (12/21) of patients with advanced solid tumors and a decrease in phosphorylated Met in one patient with multiple myeloma (PMID: 24901237). 24901237
MET positive cholangiocarcinoma predicted - sensitive Cabozantinib Phase II Emerging In a Phase II trial, higher baseline soluble Met level correlated with longer overall survival in cholangiocarcinoma patients treated with Cometriq (cabozantinib) (PMID: 28192597). 28192597
MET positive triple-receptor negative breast cancer sensitive Cabozantinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cometriq (cabozantinib) inhibited Met activity, cell growth, and invasive cellular characteristics in a human MET positive TNBC cell line in culture, and reduced tumor volume in xenograft models (PMID: 26432786). 26432786
MET positive glioblastoma multiforme sensitive Altiratinib + Bevacizumab Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Altiratinib (DCC-2701) and Avastin (bevacizumab) inhibited tumor growth and invasiveness, decreased blood vessel formation, and prolonged survival in cell line xenograft models of MET-expressing glioblastoma (PMID: 26965451). 26965451
MET positive Advanced Solid Tumor sensitive INCB028060 Phase I Actionable In a Phase I trial, INCB028060 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, as indicated by decreased whole blood Met phosphorylation level (J Clin Oncol 29: 2011 (suppl; abstr 3091)). detail...
MET positive Advanced Solid Tumor sensitive ARGX-111 Phase I Actionable In a Phase I trial, ARGX-111 demonstrated safety and resulted in some efficacy in patients with advanced solid tumors expressing MET, including a decrease in circulating tumor cells positive for MET (Journal of Clinical Oncology 33, no. 15_suppl, May 2015, 2580-2580). detail...
MET positive myeloid neoplasm predicted - sensitive Amuvatinib Preclinical - Cell culture Actionable In a preclinical study, Amuvatinib (MP470) demonstrated efficacy in reducing Met phosphorylation and inducing apoptosis in cultured myeloma cells (PMID: 24326130). 24326130
ERBB2 neg MET pos gastric adenocarcinoma no benefit Onartuzumab Phase III Actionable In a Phase III trial, addition of Onartuzumab to mFOLFOX6 did not improve clinical outcome compared to mFOLFOX6 alone in MET-positive, ERBB2 (HER2)-positive gastric/gastroesophageal junction adenocarcinoma patients (J Clin Oncol 33, 2015 (suppl; abstr 4012)). detail...
ERBB2 neg MET pos gastroesophageal junction adenocarcinoma no benefit Onartuzumab Phase III Actionable In a Phase III trial, addition of Onartuzumab to mFOLFOX6 did not improve clinical outcome compared to mFOLFOX6 alone in MET-positive, ERBB2 (HER2)-positive gastric/gastroesophageal junction adenocarcinoma patients (J Clin Oncol 33, 2015 (suppl; abstr 4012)). detail...
ERBB2 neg MET pos gastric adenocarcinoma no benefit AMG102 Phase III Actionable In a Phase III trial, addition of Rilotumumab to chemotherapy consisted of epirubicin, cisplatin and capecitabine (ECX) resulted in statistically significantly worse overall survival (9.6 vs 11.5 months) compared to ECX alone in MET-positive, ERBB2 (HER2)-positive gastric/gastroesophageal junction adenocarcinoma patients (J Clin Oncol 33, 2015 (suppl; abstr 4000)). detail...
ERBB2 neg MET pos gastric adenocarcinoma no benefit Onartuzumab + mFOLFOX6 Phase III Actionable In a Phase III trial, addition of Onartuzumab to the mFOLFOX6 chemotherapy did not improve overall survival (HR=0.82, p=0.24), progression free survival (HR=0.90, p=0.43), or objective response rate (46.1% vs 40.6%) compared to placebo in patients with Erbb2 (Her2)-negative, Met-positive gastroesophageal adenocarcinoma (PMID: 27918764). 27918764
ERBB2 neg MET pos esophagus adenocarcinoma no benefit Onartuzumab + mFOLFOX6 Phase III Actionable In a Phase III trial, addition of Onartuzumab to the mFOLFOX6 chemotherapy did not improve overall survival (HR=0.82, p=0.24), progression free survival (HR=0.90, p=0.43), or objective response rate (46.1% vs 40.6%) compared to placebo in patients with Erbb2 (Her2)-negative, Met-positive gastroesophageal adenocarcinoma (PMID: 27918764). 27918764
ERBB2 neg MET pos gastroesophageal junction adenocarcinoma no benefit AMG102 Phase III Actionable In a Phase III trial, addition of Rilotumumab to chemotherapy consisted of epirubicin, cisplatin and capecitabine (ECX) resulted in statistically significantly worse overall survival (9.6 vs 11.5 months) compared to ECX alone in MET-positive, ERBB2 (HER2)-positive gastric/gastroesophageal junction adenocarcinoma patients (J Clin Oncol 33, 2015 (suppl; abstr 4000)). detail...
MET D1228H Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET D1228H in an in vitro kinase assay (PMID: 26285778). 26285778
MET D1228H papillary renal cell carcinoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial, a patient with papillary renal cell carcinoma harboring MET D1228H demonstrated a partial response with a duration of 21.8 months when treated with Xalkori (crizotinib) (PMID: 29149761; NCT01524926). 29149761
EGFR L858R EGFR T790M MET amp MET D1231Y lung adenocarcinoma predicted - resistant Cabozantinib + Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R, EGFR T790M, MET amplification, MET D1228H, MET D1228N, MET Y1230H, and MET D1231Y demonstrated initial symptomatic improvement and lung nodule shrinkage following treatment Cometriq (Cabometyx, cabozantinib) and Tagrisso (osimertinib) in combination, but progressed after 1 month and was found to have lost MET D1228H, MET D1228N, and MET Y1230H, and to have an increased allele fraction of MET D1231Y (PMID: 29128427). 29128427
MET D1228V Advanced Solid Tumor sensitive Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V were sensitive to Cometriq (Cabometyx, cabozantinib) in culture, resulting in suppression of Met phosphorylation (PMID: 27694386). 27694386
MET D1228V Advanced Solid Tumor resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V demonstrated resistance to treatment with Savolitinib (AZD6094) in culture, resulting in sustained Met phosphorylation (PMID: 27694386). 27694386
MET D1228V Advanced Solid Tumor sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V were sensitive to Glesatinib (MGCD265) in culture, resulting in suppression of Met phosphorylation (PMID: 27694386). 27694386
MET D1228V Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V demonstrated resistance to treatment with Xalkori (crizotinib) in culture, resulting in sustained Met phosphorylation (PMID: 27694386). 27694386
MET D1228V Advanced Solid Tumor resistant Capmatinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V demonstrated resistance to treatment with Capmatinib (INC280) in culture, resulting in sustained Met phosphorylation (PMID: 27694386). 27694386
MET D1228V Advanced Solid Tumor sensitive Merestinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing MET D1228V were sensitive to Merestinib (LY2801653) in culture, resulting in suppression of Met phosphorylation (PMID: 27694386). 27694386
EGFR exon 19 del MET amp MET D1228V lung adenocarcinoma sensitive Cabozantinib + Erlotinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion, MET amplification, and MET D1228V demonstrated a strong response to the combination of Tarceva (erlotinib) and Cometriq (Cabometyx, cabozantinib), resulting in reduced tumor size (PMID: 27694386). 27694386
MET M1149T papillary renal cell carcinoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial, a patient with papillary renal cell carcinoma harboring MET M1149T demonstrated stable disease when treated with Xalkori (crizotinib) (PMID: 29149761; NCT01524926). 29149761
MET M1250T Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET M1250T in an in vitro kinase assay (PMID: 26285778). 26285778
MET negative triple-receptor negative breast cancer no benefit Cabozantinib Preclinical Actionable In a preclinical study, Cometriq (cabozantinib) treatment had no effect on the cellular outgrowth or tumor volume of a TNBC cell line negative for MET expression in culture (PMID: 26432786). 26432786
MET wild-type prostate cancer sensitive BMS-777607 Preclinical Actionable In a preclinical study, BMS-777607 (ASLAN002) demonstrated efficacy in inhibiting migration and invasion of cultured prostate cancer cells expressing wild-type Met (PMID: 20515943). 20515943
MET wild-type Advanced Solid Tumor decreased response Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in only partial growth inhibition in MET wild-type cell line xenograft models of various tumor types (PMID: 28765324). 28765324
MET wild-type bladder carcinoma decreased response Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in only partial growth inhibition in cell line xenograft models of MET wild-type urinary bladder carcinoma (PMID: 28765324). 28765324
MET wild-type prostate cancer decreased response Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in only partial growth inhibition in cell line xenograft models of MET wild-type prostate caner (PMID: 28765324). 28765324
MET wild-type cholangiocarcinoma sensitive Merestinib Preclinical - Pdx & cell culture Actionable In a preclinical study, LY2801653 inhibited phosphorylation of Met, resulting in inhibition of cholangiocarcinoma proliferation in cell culture and growth of tumors in Pdx models (PMID: 26757360). 26757360
MET wild-type pancreatic cancer decreased response Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in only partial growth inhibition in cell line xenograft models of MET wild-type pancreatic cancer (PMID: 28765324). 28765324
MET wild-type breast cancer decreased response Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment only resulted in partial growth inhibition in cell line xenograft models of MET wild-type breast cancer (PMID: 28765324). 28765324
MET wild-type colorectal cancer decreased response Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in only partial growth inhibition in cell line xenograft models of MET wild-type colorectal cancer (PMID: 28765324). 28765324
KRAS G12D MET over exp stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human gastric cancer cell line with high levels of MET expression and expressing KRAS G12D was resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26432108). 26432108
FGFR1 amp MET over exp lung cancer resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, MET overexpression and activation was identified as the mechanism mediating acquired Rogaratinib (BAY 1163877) resistance in a FGFR1 amplified lung cancer cell line in culture (PMID: 27429073). 27429073
FGFR1 amp MET over exp lung small cell carcinoma resistant BGJ398 Preclinical - Cell culture Actionable In a preclinical study, overexpression and activation of Met was identified in a small cell lung cancer cell line harboring FGFR1 amplification that acquired resistance to BGJ398 in culture (PMID: 28630215). 28630215
FGFR1 amp MET over exp lung cancer sensitive Crizotinib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Rogaratinib (BAY 1163877) and Xalkori (crizotinib) synergistically inhibited proliferation of FGFR1 amplified lung cancer cells that acquired resistance to Rogaratinib (BAY 1163877) through MET overexpression and activation in culture (PMID: 27429073). 27429073
FGFR1 amp MET over exp lung small cell carcinoma sensitive BGJ398 + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Xalkori (crizotinib) synergistically inhibited Erk signaling, resulted in growth inhibition in small cell lung carcinoma cells harboring FGFR1 amplification and Met overexpression in culture (PMID: 28630215). 28630215
FGFR1 amp MET over exp lung small cell carcinoma sensitive BGJ398 + EMD 1214063 Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and EMD 1214063 synergistically inhibited growth of small cell lung carcinoma cells harboring FGFR1 amplification and Met overexpression in culture (PMID: 28630215). 28630215
MET over exp stomach cancer sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of a human gastric cancer cell line with high levels of MET expression in culture (PMID: 26432108). 26432108
MET over exp non-small cell lung carcinoma sensitive Erlotinib + Telisotuzumab vedotin Phase I Actionable In a Phase I trial, the combination of ABBV-399 and Tarceva (erlotinib) resulted in a partial response in 31% (4/13) of non-small cell lung carcinoma patients and disease control at 12 weeks in 61.5% (8/13) of patients (J Clin Oncol 35, 2017 (suppl; abstr 2509)). detail...
MET over exp stomach cancer sensitive KRC-00715 Preclinical Actionable In a preclinical study, KRC-00715 induced cell-cycle arrest and inhibited growth of Met-over expressing gastric cancer cell lines in culture and in xenograft models, and did not inhibit growth of cell lines with low Met expression (PMID: 26801760). 26801760
MET over exp triple-receptor negative breast cancer sensitive Foretinib + Rucaparib Preclinical - Cell culture Actionable In a preclinical study, Foretinib (GSK1363089) and Rubraca (rucaparib) combination treatment resulted in enhanced growth inhibition in Met-over expressing triple-receptor negative breast cancer cells in culture (PMID: 26779812). 26779812
MET over exp lung cancer sensitive Crizotinib + Rucaparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Rubraca (rucaparib) synergized to inhibit growth of a Met-over expressing human lung cancer cell line in culture, and reduced tumor growth in xenograft models (PMID: 26779812). 26779812
MET over exp cholangiocarcinoma predicted - sensitive Cabozantinib Phase II Actionable In a Phase II trial, a cholangiocarcinoma patient with high Met expression in tumor stayed on Cometriq (cabozantinib) treatment for 278 days (PMID: 28192597). 28192597
MET over exp hepatocellular carcinoma sensitive SCC244 Preclinical - Pdx Actionable In a preclinical study, hepatocellular carcinoma patient-derived xenograft (PDX) models overexpressing MET were sensitive to SCC244, demonstrating a complete response in one and partial response in eleven (PMID: 29237805). 29237805
MET over exp lung cancer sensitive SYM015 Preclinical - Pdx & cell culture Actionable In a preclinical study, SYM015 treatment reduced Met expression and phosphorylation, resulted in growth inhibition in culture, and tumor elimination in both cell line xenograft and patient-derived xenograft (PDX) models of lung cancer with high Met expression (PMID: 28679766). 28679766
MET over exp triple-receptor negative breast cancer decreased response Rucaparib Preclinical - Cell culture Actionable In a preclinical study, triple-receptor negative breast cancer cell lines overexpressing Met demonstrated decreased sensitivity to Rubraca (rucaparib) induced growth and colony formation inhibition in culture (PMID: 26779812). 26779812
MET over exp lung squamous cell carcinoma sensitive EMD 1214063 Preclinical - Cell culture Actionable In a preclinical study, EMD 1214063 inhibited Met phosphorylation and cell viability of Met over-expressing lung squamous cell carcinoma cells in culture (PMID: 26358474). 26358474
MET over exp colorectal cancer resistant Panitumumab Preclinical - Cell culture Actionable In a preclinical study, over expression of MET conferred resistance to Vectibix (panitumumab) in colorectal cancer cell lines in culture (PMID: 23729478). 23729478
MET over exp triple-receptor negative breast cancer sensitive Crizotinib + Rucaparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Rubraca (rucaparib) synergized to inhibit growth of Met-over expressing human triple-receptor negative breast cancer cell lines in culture, and reduced tumor growth in xenograft models (PMID: 26779812). 26779812
MET over exp lung adenocarcinoma sensitive Merestinib Preclinical - Cell line xenograft Actionable In a preclinical study, Merestinib (LY2801653) demonstrated anti-tumor activity in cell line xenograft models of lung adenocarcinoma with Met over expression (PMID: 23275061). 23275061
MET over exp triple-receptor negative breast cancer unknown BKM120 + Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, triple-receptor negative breast cancer xenograft models overexpressing MET demonstrated stable disease when treated with the combination therapy, BKM120 and Xalkori (crizotinib) (PMID: 29203461). 29203461
MET over exp glioblastoma multiforme predicted - sensitive Altiratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited Met phosphorylation and viability of several Met over expressing glioblastoma cell lines in culture and inhibited tumor growth in cell line xenograft models (PMID: 26965451). 26965451
MET over exp non-small cell lung carcinoma sensitive SCC244 Preclinical - Pdx Actionable In a preclinical study, non-small cell lung carcinoma patient-derived xenograft (PDX) models harboring MET overexpression were sensitive to SCC244, demonstrating inhibition of tumor growth and nine partial responses (PMID: 29237805). 29237805
MET over exp colorectal cancer sensitive Cetuximab + JNJ 38877605 Preclinical - Cell culture Actionable In a preclinical study, the addition of JNJ-38877605 to Erbitux (cetuximab) treatment overcame Erbitux (cetuximab) resistance in colorectal cancer cell lines over expressing MET in culture (PMID: 23729478). 23729478
MET over exp lung papillary adenocarcinoma sensitive Telisotuzumab vedotin Preclinical - Cell culture Actionable In a preclinical study, treatment with ABBV-399 resulted in complete response in a MET-over expressing papillary lung adenocarcinoma cell line xenograft model (PMID: 27573171). 27573171
MET over exp colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, over expression of MET conferred resistance to Erbitux (cetuximab) in colorectal cancer cell lines in culture (PMID: 23729478). 23729478
MET over exp stomach cancer sensitive SYM015 Preclinical - Pdx & cell culture Actionable In a preclinical study, SYM015 treatment reduced Met expression and phosphorylation, resulted in growth inhibition in culture, and tumor elimination in patient-derived xenograft (PDX) models of gastric cancer with high Met expression (PMID: 28679766). 28679766
MET over exp stomach carcinoma sensitive EMD 1214063 Preclinical - Cell culture Actionable In a preclinical study, EMD 1214063 inhibited Met phosphorylation and cell viability of Met over-expressing gasric carcinoma cell lines in culture, regardless of their TP53 status (PMID: 26358474). 26358474
MET over exp lung small cell carcinoma sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited growth of small cell lung carcinoma lines over-expressing MET (PMID: 25122427). 25122427
MET over exp hepatocellular carcinoma sensitive Tepotinib Preclinical - Pdx Actionable In a preclinical study, Tepotinib (MSC2156119J) treatment resulted in tumor regression in patient-derived xenograft models of hepatocellular cancer with high Met expression level (PMID: 25256830). 25256830
MET over exp lung adenocarcinoma predicted - sensitive Telisotuzumab vedotin Preclinical - Pdx Actionable In a preclinical study, ABBV-399 demonstrated efficacy in MET-expressing lung adenocarcinoma patient-derived xenograft (PDX) models, with the PDX model with higher MET expression levels showing improved tumor growth delay (PMID: 27573171). 27573171
MET over exp melanoma sensitive XL147 Preclinical Actionable In a preclinical study, XL147 inhibited migration and growth of mouse melanoma cells with MET over expression in culture (PMID: 25637314). 25637314
MET over exp triple-receptor negative breast cancer sensitive Foretinib + Veliparib Preclinical - Cell line xenograft Actionable In a preclinical study, Foretinib (GSK1363089) and Veliparib (ABT-888) worked synergistically to inhibit growth of Met-over expressing triple-receptor negative breast cancer cells in culture, and reduced tumor growth in xenograft models (PMID: 26779812). 26779812
MET over exp non-small cell lung carcinoma sensitive Telisotuzumab vedotin Preclinical - Cell culture Actionable In a preclinical study, ABBV-399 inhibited growth of MET over expressing non-small cell lung cancer cell lines in culture (PMID: 27573171). 27573171
MET over exp non-small cell lung carcinoma sensitive Telisotuzumab vedotin Phase I Actionable In a Phase I trial, ABBV-399 resulted in a partial response in 19% (3/16) of patients with non-small cell lung carcinoma while 37.5% (6/16) of patients experienced disease control at 12 weeks (J Clin Oncol 35, 2017 (suppl; abstr 2509)). detail...
MET over exp colorectal cancer sensitive JNJ 38877605 + Panitumumab Preclinical - Cell culture Actionable In a preclinical study, the addition of JNJ-38877605 to Vectibix (panitumumab) treatment overcame Vectibix (panitumumab) resistance in colorectal cancer cell lines over expressing MET in culture (PMID: 23729478). 23729478
MET over exp stomach cancer sensitive Merestinib Preclinical - Cell line xenograft Actionable In a preclinical study, LY2801653 blocked tumor growth in a gastric cancer cell line xenograft model over expressing Met (PMID: 23275061). 23275061
MET over exp stomach cancer sensitive KRC-00509 Preclinical Actionable In a preclinical study, KRC-00509 induced cell-cycle arrest and inhibited growth of Met-over expressing gastric cancer cell lines in culture, and did not inhibit growth of cell lines with low Met expression (PMID: 26801760). 26801760
MET over exp breast cancer sensitive Crizotinib + Rucaparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Rubraca (rucaparib) synergized to inhibit growth of a Met-over expressing human breast cancer cell line in culture, and reduced tumor growth in xenograft models (PMID: 26779812). 26779812
EGFR wild-type MET over exp non-small cell lung carcinoma sensitive Capmatinib Phase I Actionable In a Phase I trial, Capmatinib (INC280) treatment resulted in partial response in 29% (5/17) of EGFR wild-type, MET over-expressing non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9067)). detail...
BRCA1 dec exp MET over exp triple-receptor negative breast cancer no benefit Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca1 expression via shRNA knockdown did not sensitize triple-receptor negative breast cancer cells with Met over expression to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) inhibited tumor growth and reduced ERK signaling in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive INC280 + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination of Mekinist (trametinib) and Capmatinib (INC280) induced tumor regression in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) inhibited tumor growth and reduced ERK signaling in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRCA2 dec exp MET over exp triple-receptor negative breast cancer no benefit Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca2 expression via shRNA knockdown did not sensitize triple-receptor negative breast cancer cells with Met overexpression to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
MET amp over exp stomach carcinoma sensitive K252a Preclinical Actionable In preclinical studies, a MET amplified, gastric carcinoma cell over expressing Met was sensitive to K252a treatment in both culture and mouse model experiments (PMID: 12118367). 12118367
MET amp over exp stomach cancer sensitive Altiratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Altiratinib (DCC-0701) inhibited Met phosphorylation and proliferation of a gastric cancer cell line with MET amplification and over expression in culture, and inhibited tumor growth and induced tumor regression in xenograft models (PMID: 26285778). 26285778
MET amp over exp non-small cell lung carcinoma sensitive Altiratinib Preclinical - Cell culture Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited Met phosphorylation and proliferation of a non-small cell lung cancer cell line with MET amplification and overexpression in culture (PMID: 26285778). 26285778
MET over exp TP53 dec exp stomach carcinoma sensitive EMD 1214063 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, shRNA knock-down of Tp53 in Met over-expressing gastric carcinoma cells enhanced sensitivity to the combination of EMD 1214063 and radiation in culture (PMID: 26358474). 26358474
MET L1213V cancer resistant SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET L1213V showed resistance to SU11274 treatment (PMID: 15064724). 15064724
MET D1228N Advanced Solid Tumor predicted - sensitive BMS-777607 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to D1228N in humans) were sensitive to treatment with BMS-777607 (ASLAN002), demonstrating inhibition of cell growth in culture (PMID: 28396313). 28396313
MET D1228N Advanced Solid Tumor predicted - resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to MET D1228N in humans) were resistant to treatment with Savolitinib (AZD6094), demonstrating sustained cell growth in culture (PMID: 28396313). 28396313
MET D1228N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to MET D1228N in humans) were resistant to treatment with Xalkori (crizotinib), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in mouse models (PMID: 28396313). 28396313
MET D1228N Advanced Solid Tumor predicted - resistant Capmatinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to MET D1228N in humans) were resistant to treatment with Capmatinib (INC280), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in mouse models (PMID: 28396313). 28396313
MET D1228N Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET D1228N in an in vitro kinase assay (PMID: 26285778). 26285778
MET D1228N Advanced Solid Tumor predicted - sensitive Cabozantinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET D1226N (corresponds to MET D1228N in humans) were sensitive to treatment with Cometriq (Cabometyx, cabozantinib), demonstrating inhibition of cell growth in culture and tumor growth inhibition in mouse models (PMID: 28396313). 28396313
MET D1228N Advanced Solid Tumor sensitive Merestinib Preclinical - Cell culture Actionable In a preclinical study, Merestinib (LY2801653) inhibited growth of transformed cells over expressing MET D1228N in culture (PMID: 23275061). 23275061
MET F1200I papillary renal cell carcinoma predicted - sensitive Crizotinib Phase II Actionable In a Phase II trial, a patient with papillary renal cell carcinoma harboring MET G1163T demonstrated a partial response with a duration of 37.3 months when treated with Xalkori (crizotinib) (PMID: 29149761; NCT01524926). 29149761
MET V1206L cancer sensitive SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET V1206I demonstrated sensitivity to SU11274 treatment (PMID: 19783361). 19783361
MET E168D Advanced Solid Tumor sensitive SU11274 Preclinical Actionable In a preclinical study, SU11274 induced apoptosis of cells expressing MET E168D, which demonstrated increased sensitivity compared to cells expressing wild-type MET (PMID: 19723643). 19723643
ERBB2 over exp MET amp MET R988C stomach cancer predicted - resistant Trastuzumab Clinical Study Actionable In a clinical study, assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) gastric or gastroesophageal cancer patients identified MET R988C and amplification of MET in 1 patient demonstrating primary resistance to Herceptin (trastuzumab) (PMID: 29208673). 29208673
KIT S476I MET R988C gastrointestinal stromal tumor sensitive Bevacizumab + Sorafenib Clinical Study Actionable In a clinical case study, a GIST patient harboring KIT S476I and MET R988C demonstrated sensitivity to the combination treatment, Nexavar (sorafenib) and Avastin (bevacizumab), resulting in stable disease for 6 months (PMID: 25363205). 25363205
MET R988C Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing MET R998C demonstrated sensitivity to Xalkori (crizotinib) in culture (PMID: 17483355). 17483355
MET Y1248H cancer resistant SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET Y1248H showed resistance to SU11274 treatment (PMID: 15064724). 15064724
MET V1238I cancer sensitive SU11274 Preclinical Actionable In a preclinical study, a cell line expressing MET V1238I demonstrated sensitivity to SU11274 treatment (PMID: 19783361). 19783361
ERBB2 over exp MET amp stomach cancer predicted - resistant Trastuzumab Clinical Study Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tissue from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified MET amplification in 1 patient demonstrating primary resistance to Herceptin (trastuzumab) (PMID: 29208673). 29208673
KRAS G12D MET amp esophageal carcinoma resistant AMG 337 Clinical Study Actionable In a clinical case study, a patient with a MET amplified esophageal carcinoma that initially responded to AMG 337, developed resistance upon emergence of KRAS G12D (PMID: 26432108). 26432108
EGFR exon 19 del MET amp non-small cell lung carcinoma resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, amplification of MET conferred resistance to Iressa (gefitinib) in non-small cell lung cancer cells harboring an EGFR exon 19 deletion mutation in culture (PMID: 17463250). 17463250
EGFR exon 19 del MET amp lung adenocarcinoma resistant Afatinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification was resistant to Gilotrif (afatinib) (PMID: 27694386). 27694386
EGFR exon 19 del MET amp non-small cell lung carcinoma sensitive JNJ-61186372 Preclinical - Cell line xenograft Actionable In a preclinical study, JNJ-61186372 inhibited tumor growth in Tarceva (erlotinib)-resistant non-small cell lung cancer cell line xenograft models harboring an EGFR exon 19 deletion and MET amplification (PMID: 27216193). 27216193
EGFR exon 19 del MET amp lung adenocarcinoma sensitive Osimertinib + Savolitinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification demonstrated a near complete response when treated with the combination of Savolitinib (AZD6094) and Tagrisso (osimertinib), however, after 36 weeks presented with progression (PMID: 27694386). 27694386
EGFR exon 19 del MET amp lung adenocarcinoma resistant Erlotinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring an EGFR exon 19 deletion and MET amplification was resistant to Tarceva (erlotinib) (PMID: 27694386). 27694386
BRAF V600E EGFR exon 19 del MET amp lung adenocarcinoma resistant Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR exon 19 deletion treated with Tagrisso (osimertinib) showed progression after 16 months and was subsequently found to have acquired BRAF V600E and MET amplification (PMID: 29596911). 29596911
KRAS G12V MET amp carcinoma predicted - sensitive Crizotinib Clinical Study Actionable In a clinical case study, a patient with a carcinoma of unknown primary harboring MET amplification and KRAS G12V demonstrated a durable response following treatment with Xalkori (crizotinib) (PMID: 25232318). 25232318
EGFR L858R MET amp non-small cell lung carcinoma sensitive CO1686 + Crizotinib Preclinical - Pdx Actionable In a preclinical study, the combination of Rociletinib (CO-1686) and Xalkori (crizotinib) overcame resistance to Rociletinib (CO-1686) in a patient-derived xenograft model of non-small cell lung cancer harboring EGFR L858R and MET amplification, resulting in tumor growth inhibition (PMID: 27283993). 27283993
EGFR exon 19 del EGFR T790M MET amp lung adenocarcinoma predicted - sensitive Crizotinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring an EGFR exon 19 deletion and EGFR T790M and resistance to Tagrisso (osimertinib) following acquired MET amplification, demonstrated some improvement in symptoms with Xalkori (crizotinib) treatment (PMID: 27393507). 27393507
EGFR exon 19 del EGFR T790M MET amp lung adenocarcinoma resistant Osimertinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring an EGFR exon 19 deletion and EGFR T790M developed resistance to Tagrisso (osimertinib), and was found to have acquired high level amplification of MET (PMID: 27393507). 27393507
EGFR act mut MET amp lung cancer sensitive SYM015 Preclinical - Pdx Actionable In a preclinical study, SYM015 treatment resulted in tumor growth inhibition in patient-derived xenograft (PDX) models of MET-amplified lung cancer harboring EGFR activating mutations (PMID: 28679766). 28679766
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 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
FGFR1 amp MET amp lung cancer resistant AZD4547 Preclinical - Cell culture Actionable In a preclinical study, MET amplification was identified as the mechanism mediating acquired AZD4547 resistance in a FGFR1 amplified lung cancer cell line in culture (PMID: 27429073). 27429073
FGFR1 amp MET amp lung cancer sensitive AZD4547 + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, AZD4547 and Xalkori (crizotinib) synergistically inhibited proliferation of FGFR1 amplified lung cancer cells that acquired resistance to AZD4547 through MET amplification in culture (PMID: 27429073). 27429073
FGFR1 amp MET amp lung squamous cell carcinoma predicted - resistant BGJ398 Phase I Actionable In a Phase I trial, MET amplification was detected in a squamous cell lung cancer patient harboring FGFR1 amplification whose disease relapsed after 17 months of BGJ398 treatment, supporting a role of MET amplification in drug resistance in FGFR1-amplified lung cancer (PMID: 28630215). 28630215
MET amp TP53 del breast cancer sensitive Crizotinib Preclinical Actionable In a preclinical study, Xalkori (crizotinib) treatment resulted in complete tumor regression in transplant models of TP53-null-luminal breast cancer harboring MET amplification (PMID: 27149990). 27149990
EGFR amp MET amp non-small cell lung carcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical case study, two patients with non-small cell lung cancer harboring EGFR amplification and EGFR T790M progressed after Tagrisso (osimertinib) treatment, and were found to have lost the EGFR T790M and acquired MET amplification (PMID: 30268451). 30268451
EGFR amp MET amp non-small cell lung carcinoma predicted - resistant Gefitinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung cancer harboring EGFR amplification progressed after Iressa (gefitinib) treatment, and was found to have acquired MET amplification (PMID: 30268451). 30268451
EGFR amp MET amp non-small cell lung carcinoma predicted - resistant Erlotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung cancer harboring EGFR amplification progressed after Tarceva (erlotinib) treatment, and was found to have acquired MET amplification (PMID: 30268451). 30268451
EGFR amp MET amp esophagus adenocarcinoma sensitive Crizotinib + Lapatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Tykerb (lapatinib) worked synergistically to inhibit growth of an esophageal adenocarcinoma cell line with EGFR and MET copy number gain in culture (PMID: 27595477). 27595477
EGFR T790M MET amp non-small cell lung carcinoma resistant CO1686 Clinical Study Actionable In an analysis of EGFR T790M-positive non-small cell lung cancer patients, emergence of MET amplification was identified in 26% (28/43) of patients with acquired resistance to Rociletinib (CO1686), and patients with MET amplification prior to Rociletinib (CO1686) treatment demonstrated a decreased response compared to patients without MET amplification (PMID: 27283993). 27283993
EGFR T790M MET amp lung adenocarcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, expression of EGFR T790M in MET-amplified lung adenocarcinoma cells resulted in resistance to Tagrisso (osimertinib) in culture, consistent with MET amplification identified in tumor samples of lung adenocarcinoma patients harboring EGFR T790M that developed resistance to Tagrisso (osimertinib) (PMID: 27252416). 27252416
EGFR T790M MET amp lung adenocarcinoma resistant CO1686 Preclinical Actionable In a preclinical study, expression of EGFR T790M in MET-amplified lung adenocarcinoma cells resulted in resistance to Rociletinib (CO-1686) in culture, consistent with MET amplification identified in tumor samples of lung adenocarcinoma patients harboring EGFR T790M that developed resistance to Rociletinib (CO-1686) (PMID: 27252416). 27252416
MET amp stomach cancer sensitive KTN0073-IgG2 Preclinical - Cell line xenograft Actionable In a preclinical study, KTN0073-IgG2 inhibited MET phosphorylation and induced MET degradation, and inhibited growth of a MET-amplified gastric cancer cell line in culture and in xenograft models (PMID: 27550450). 27550450
MET amp non-small cell lung carcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung cancer harboring EGFR amplification and EGFR T790M progressed after Tagrisso (osimertinib) treatment, and was found to have lost the EGFR mutations and acquired a MET amplification (PMID: 30268451). 30268451
MET amp non-small cell lung carcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical case study, two patients with non-small cell lung cancer harboring EGFR T790M progressed after Tagrisso (osimertinib) treatment, and was found to have lost EGFR T790M and acquired MET amplification (PMID: 30268451). 30268451
MET amp stomach carcinoma sensitive EMD 1214063 Preclinical - Cell line xenograft Actionable In a preclinical study, EMD 1214063 induced tumor regression in mouse cell line xenograft models of gastric carcinoma harboring MET amplification (PMID: 23553846). 23553846
MET amp non-small cell lung carcinoma predicted - sensitive Merestinib Preclinical - Pdx Actionable In a preclinical study, Merestinib (LY2801653) treatment resulted in growth inhibition in patient-derived xenograft (PDX) models of MET-amplified non-small cell lung carcinoma that were resistant to Egfr inhibitors (Cancer Res 2010;70(8 Suppl):Abstract nr 3611). detail...
MET amp non-small cell lung carcinoma sensitive Selumetinib + BEZ235 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) in combination with BEZ235, synergistically inhibited proliferation of an Iressa (gefitinib)-resistant NSCLC cell line harboring MET amplification in culture and in cell line xenograft models (PMID: 24939055). 24939055
MET amp esophagus adenocarcinoma sensitive AMG 337 Clinical Study Actionable In a clinical case study, a patient with MET amplified esophageal adenocarcinoma had a partial response to AMG 337 therapy after 2 months of treatment (PMID: 26432108). 26432108
MET amp stomach cancer sensitive TAS-115 Preclinical Actionable In a preclinical study, MET amplified gastric cancer cell lines were sensitive to TAS-115, resulting in suppression of cell proliferation in culture (PMID: 24140932). 24140932
MET amp Advanced Solid Tumor sensitive SYM015 Preclinical - Pdx & cell culture Actionable In a preclinical study, Sym015 inhibited growth of cancer cell lines with MET amplification in culture, and inhibited tumor growth in MET-amplified patient-derived xenograft (PDX) models (Cancer Res July 15 2016 (76) (14 Supplement) 1219). detail...
MET amp Advanced Solid Tumor sensitive ABT-700 Phase I Actionable In a Phase I trial, ABT-700 demonstrated safety and preliminary efficacy in patients with MET-amplified advanced solid tumors, including a patient with ovarian cancer (J Clin Oncol 32:5s, 2014 (suppl; abstr 2507)). detail...
MET amp non-small cell lung carcinoma predicted - sensitive Alvespimycin Preclinical - Cell line xenograft Actionable In a preclinical study, disruption of multiple kinases with Hsp90 inhibitor Alvespimycin inhibited survival of MET amplified non-small cell lung cancer cells that acquired resistance to SGX532 through activation of multiple kinase signaling pathways in culture and in cell line xenograft models (PMID: 26483207). 26483207
MET amp colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical study, MET amplification was associated with resistance to Erbitux (cetuximab) in 2 colorectal cancer patients, and in patient-derived xenograft (PDX) models (PMID: 23729478). 23729478
MET amp lung squamous cell carcinoma sensitive SCC244 Preclinical - Cell line xenograft Actionable In a preclinical study, SCC244 inhibited Met activity, downstream signaling, and cell proliferation in lung squamous cell carcinoma cells harboring MET amplification in culture, and inhibited tumor growth in cell line xenograft models (PMID: 29237805). 29237805
MET amp stomach cancer no benefit FF-284 Preclinical - Cell line xenograft Actionable In a preclinical study, Debio 1347 did not inhibit tumor growth in cell line xenograft models of MET amplified gastric cancer (PMID: 26438159). 26438159
MET amp non-small cell lung carcinoma sensitive EMD 1214063 Preclinical - Cell line xenograft Actionable In a preclinical study, EMD 1214063 induced tumor regression in mouse cell line xenograft models of non-small cell lung carcinoma harboring MET amplification (PMID: 23553846). 23553846
MET amp non-small cell lung carcinoma sensitive Capmatinib Phase I Actionable In a Phase I trial, Capmatinib (INC280) treatment resulted in partial response in 63% (5/8) of MET amplified non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9067)). detail...
MET amp non-small cell lung carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring MET amplification in culture (PMID: 26090892). 26090892
MET amp stomach cancer sensitive SCC244 Preclinical - Cell line xenograft Actionable In a preclinical study, SCC244 inhibited Met activity, downstream signaling, and cell proliferation in gastric cancer cells harboring MET amplification in culture, and inhibited tumor growth in cell line xenograft models (PMID: 29237805). 29237805
MET amp Advanced Solid Tumor sensitive Emibetuzumab Preclinical Actionable In a preclinical study, Emibetuzumab (LY2875358) treatment inhibited MET activation and proliferation of tumor cells with MET amplification in culture, and inhibited growth in MET-amplified tumor xenograft models (PMID: 25231402). 25231402
MET amp non-small cell lung carcinoma sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 suppressed the growth of an Iressa (gefitinib)-resistant NSCLC cell line with MET amplification (PMID: 24939055). 24939055
MET amp Advanced Solid Tumor sensitive Tepotinib Phase I Actionable In a Phase I study, Tepotinib (MSC2156119J) demonstrated safety and preliminary efficacy in advanced solid tumor patients with MET amplification (JCO, Vol 33, No 15_suppl (May 20 Supplement), 2015: 2591). detail...
MET amp stomach cancer sensitive M-COPA Preclinical - Cell line xenograft Actionable In a preclinical study, M-COPA reduced Met cell surface expression and downstream signaling and decreased growth of MET-amplified gastric cancer cell lines in culture, and demonstrated antitumor activity in MET-amplified gastric cancer cell line xenograft models (PMID: 27197184). 27197184
MET amp stomach cancer sensitive AMG 337 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 337 inhibited growth of gastric cancer cell lines in culture, and inhibited growth and induced regression of tumors in MET-amplified gastric cancer cell line xenograft models (PMID: 27196782). 27196782
MET amp stomach cancer sensitive SGX523 Preclinical - Cell line xenograft Actionable In a preclinical study, SGX523 inhibited Met signaling and proliferation of MET amplified gastric cancer cells in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 19934279). 19934279
MET amp Advanced Solid Tumor decreased response AMG 337 Clinical Study Actionable In a retrospective study, advanced solid tumor patients harboring MET amplification only achieved stable disease in 29% (2/7) of the population, while MET-nonamplified patients achieved partial response in 10% (14/134) and stable disease in 36% (48/134) of the population, when treated with Met inhibitors including AMG 337 and EMD 1204831 (PMID: 25326232). 25326232
MET amp non-small cell lung carcinoma predicted - sensitive PP-121 Preclinical - Cell culture Actionable In a preclinical study, the multitarget kinase inhibitor PP-121 inhibited survival of MET amplified non-small cell lung cancer cells that acquired resistance to SGX532 through activation of multiple kinase signaling pathways in culture (PMID: 26483207). 26483207
MET amp lung cancer sensitive Golvatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Golvatinib (E7050) inhibited Met and Kdr (Vegfr2) phosphorylation, resulted in growth inhibition of lung cancer cells in culture and tumor regression in cell line xenograft models (PMID: 19832844). 19832844
MET amp stomach cancer sensitive ARGX-111 Phase I Actionable In a Phase I trial, a gastric cancer patient harboring MET amplification was sensitive to treatment with ARGX-111, demonstrating stable disease, a metabolic response, and a decrease in circulating tumor cells (Journal of Clinical Oncology 33, no. 15_suppl (May 2015) 2580-2580). detail...
MET amp Advanced Solid Tumor predicted - sensitive SAR125844 Phase I Actionable In a Phase I trial, SAR125844 treatment in advanced solid tumor patients harboring a MET amplification was well-tolerated and resulted in a partial response in 17% (5/29) of patients, including patients with non-small cell lung carcinoma, and stable disease in 59% (17/29) of patients (PMID: 29145039; NCT01391533). detail... 29145039
MET amp non-small cell lung carcinoma sensitive Crizotinib Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) inhibited tumor grow in patient-derived xenograft models of MET amplified non-small cell lung cancer (PMID: 26483207). 26483207
MET amp non-small cell lung carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for non-small cell lung cancer patients with high level MET amplification (NCCN.org). detail...
MET amp Advanced Solid Tumor decreased response EMD 1204831 Clinical Study Actionable In a retrospective study, advanced solid tumor patients harboring MET amplification only achieved stable disease in 29% (2/7) of the population, while MET-nonamplified patients achieved partial response in 10% (14/134) and stable disease in 36% (48/134) of the population, when treated with Met inhibitors including AMG 337 and EMD 1204831 (PMID: 25326232). 25326232
MET amp colorectal cancer sensitive JNJ 38877605 Preclinical - Pdx Actionable In a preclinical study, JNJ-38877605 inhibited tumor growth in colorectal cancer patient-derived xenograft models with MET amplification (PMID: 23729478). 23729478
MET amp lung cancer sensitive SAR125844 Preclinical - Cell culture Actionable In a preclinical study, SAR125844 inhibited Met signaling, leading to growth inhibition of MET amplified lung cancer cells in culture (PMID: 25504634). 25504634
MET amp stomach cancer sensitive Telisotuzumab vedotin Preclinical - Cell line xenograft Actionable In a preclinical study, ABBV-399 inhibited growth of MET-amplified gastric cancer cell in culture, and induced tumor regression in a MET-amplified gastric cancer cell line xenograft model (PMID: 27573171). 27573171
MET amp esophageal cancer sensitive AMG 337 Clinical Study Actionable In clinical case studies, patients with MET amplified esophageal cancer responded to AMG 337 therapy (PMID: 26432108). 26432108
MET amp non-small cell lung carcinoma sensitive SGX523 Preclinical - Cell culture Actionable In a preclinical study, SGX523 inhibited survival of MET-amplified non-small cell lung cancer cells in culture (PMID: 26483207). 26483207
MET amp stomach cancer sensitive SAR125844 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR125844 inhibited Met signaling leading to growth inhibition of MET amplified gastric cancer cell lines in culture and in xenograft models (PMID: 25504634). 25504634
MET amp stomach cancer sensitive Golvatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Golvatinib (E7050) inhibited Met and Kdr (Vegfr2) phosphorylation, resulted in growth inhibition of gastric cancer cell lines in culture and in cell line xenograft models (PMID: 19832844). 19832844
MET amp hepatocellular carcinoma sensitive AMG 337 Preclinical - Pdx & cell culture Actionable In a preclinical study, AMG 337 inhibited Met phosphorylation and growth of hepatocellular carcinoma (HCC) cell lines with MET amplification in culture, and inhibited tumor growth in MET-amplified HCC patient-derived xenograft models (PMID: 27196749). 27196749
MET amp non-small cell lung carcinoma sensitive SCC244 Preclinical - Pdx Actionable In a preclinical study, non-small cell lung carcinoma patient-derived xenograft models harboring MET amplification were sensitive to SCC244, demonstrating inhibition of tumor growth and stable disease (PMID: 29237805). 29237805
MET amp non-small cell lung carcinoma predicted - sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, the multitarget kinase inhibitor Sprycel (dasatinib) inhibited survival of MET amplified non-small cell lung cancer cells that acquired resistance to SGX532 through activation of multiple kinase signaling pathways in culture (PMID: 26483207). 26483207
MET amp Advanced Solid Tumor not applicable N/A Clinical Study Emerging In a retrospective study, advanced solid tumor patients harboring MET amplification demonstrated worse overall survival (7.23 months) comparing to patients without MET amplification (8.62 months) (PMID: 25326232), suggesting that this may serve as a future prognostic biomarker. 25326232
MET amp liver cancer sensitive Crizotinib Preclinical - Pdx Actionable In a preclinical study, Xalkori (crizotinib) inhibited tumor grow in patient-derived xenograft models of MET amplified liver cancer (PMID: 26483207). 26483207
MET amp stomach cancer sensitive Glesatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Glesatinib (MGCD265) treatment resulted in tumor regression in MET-amplified gastric cancer cell line xenograft models (PMID: 28765324). 28765324
MET amp stomach cancer sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of gastric cancer cell lines harboring MET amplification in culture (PMID: 26090892). 26090892
MET amp non-small cell lung carcinoma sensitive KTN0073-IgG2 Preclinical - Cell culture Actionable In a preclinical study, KTN0073-IgG2 inhibited MET phosphorylation and induced MET degradation, and inhibited proliferation of a MET-amplified non-small cell lung cancer cell line in culture (PMID: 27550450). 27550450
MET amp Advanced Solid Tumor predicted - sensitive Capmatinib Phase I Actionable In a Phase I trial, INC280 displayed safety and preliminary efficacy in patients with MET dependent solid tumors (J Clin Oncol 32:5s, 2014 (suppl; abstr 2520)). detail...
MET amp non-small cell lung carcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) suppressed the growth of an Iressa (gefitinib)-resistant NSCLC cell line with MET amplification (PMID: 24939055). 24939055
MET amp lung cancer sensitive AMG 337 Preclinical - Cell culture Actionable In a preclinical study, AMG 337 inhibited growth of MET-amplified lung cancer cell lines in culture (PMID: 27196782). 27196782
MET amp lung cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, Glesatinib (MGCD265) inhibited Met phosphorylation and growth of MET-amplified lung cancer cells in culture (PMID: 28765324). 28765324
MET amp non-small cell lung carcinoma predicted - sensitive Ganetespib Preclinical - Cell culture Actionable In a preclinical study, disruption of multiple kinases with Hsp90 inhibitor Ganetespib inhibited survival of MET amplified non-small cell lung cancer cells that acquired resistance to SGX532 through activation of multiple kinase signaling pathways in culture (PMID: 26483207). 26483207
MET amp papillary renal cell carcinoma sensitive Savolitinib Phase II Actionable In a Phase II trial, treatment with Savolitinib (AZD6094) resulted in an overall response rate (ORR) of 18% (8/44, all partial responses) in the subgroup of patients with MET-driven papillary renal cell carcinoma (PRCC), which included patients with MET amplification, compared to an ORR of 0% (0/46) in patients with MET-independent PRCC (PMID: 28644771; NCT02127710). 28644771
MET amp papillary renal cell carcinoma sensitive Savolitinib Preclinical - Pdx Actionable In a preclinical study, Savolitinib (AZD6094) demonstrated antitumor activity in patient-derived papillary renal cell carcinoma xenograft models harboring MET amplification (PMID: 25779944). 25779944
KRAS G12A MET amp lung cancer resistant AMG 337 Preclinical - Cell culture Actionable In a preclinical study, a MET-amplified lung cancer cell line harboring KRAS G12A was not sensitive to growth inhibition by AMG 337 in culture (PMID: 27196782). 27196782
KRAS G12A MET amp lung cancer resistant SAR125844 Preclinical - Cell culture Actionable In a preclinical study, MET amplified lung cancer cells harboring KRAS G12A were insensitive to SAR125844-mediated growth inhibition in culture (PMID: 25504634). 25504634
EGFR mut MET amp non-small cell lung carcinoma predicted - sensitive Crizotinib Clinical Study Actionable In a clinical study, Xalkori (crizotinib) treatment resulted in partial response (PR) in 50% (4/8) of patients with EGFR mutant non-small cell lung cancer that acquired MET amplification after EGFR TKI therapy, although the response was short-lived, with a median progression-free survival of 3.5 months in patients achieved PR (PMID: 30268451). 30268451
EGFR mut MET amp lung adenocarcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, amplification of MET was identified in a lung adenocarcinoma cell line harboring EGFR mutation that acquired resistance to Tarceva (erlotinib) in culture (PMID: 28630215). 28630215
EGFR mut MET amp lung adenocarcinoma sensitive Erlotinib + EMD 1214063 Preclinical - Cell culture Actionable In a preclinical study, Tarceva (erlotinib) and EMD 1214063 synergistically inhibited growth of lung carcinoma cells harboring EGFR mutation and Met amplification in culture (PMID: 28630215). 28630215
EGFR mut MET amp non-small cell lung carcinoma sensitive Capmatinib + Gefitinib Phase Ib/II Actionable In a Phase Ib/II trial, Capmatinib (INC280) and Iressa (gefitinib) combination treatment resulted in an objective response rate of 27% (43/161) in non-small cell lung cancer patients harboring EGFR mutations and MET dysregulation (amplification or overexpression), with an objective response rate of 47% in Phase II patients with a MET gene copy number greater than 6 (PMID: 30156984). 30156984
ERBB2 amp MET amp gastroesophageal junction adenocarcinoma sensitive Crizotinib + Lapatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Tykerb (lapatinib) inhibited the growth of gastroesophageal adenocarcinoma cells with ERBB2 (HER2) and MET amplification in culture (PMID: 25350844). 25350844
ERBB2 amp MET amp esophageal carcinoma sensitive Crizotinib + Lapatinib Preclinical - Cell culture Actionable In a preclinical study, a human esophageal carcinoma cell line harboring amplification of ERBB2 (HER2) and MET was sensitive to inhibition by Tykerb (lapatinib) and Xalkori (crizotinib) in culture (PMID: 26432108). 26432108
ERBB2 amp MET amp gastric adenocarcinoma resistant Trastuzumab + Fluorouracil + Leucovorin + Oxaliplatin Clinical Study Actionable In a clinical case study, a patient with ERBB2 (HER2) and MET amplified gastric adenocarcinoma was insensitive to treatment with Herceptin (trastuzumab) and FOLFOX (PMID: 26432108). 26432108
ERBB2 amp MET amp esophageal carcinoma resistant Lapatinib Preclinical Actionable In a preclinical study, a human esophageal carcinoma cell line harboring amplification of ERBB2 and MET was resistant to Tykerb (lapatinib) in culture (PMID: 26432108). 26432108
ERBB2 amp MET amp gastric adenocarcinoma sensitive Crizotinib + Trastuzumab + Paclitaxel Clinical Study Actionable In a clinical case study, a patient with ERBB2 (HER2) and MET co-amplified gastric adenocarcinoma had near complete regression of the disease after 2 months of treatment with Herceptin (trastuzumab), Xalkori (crizotinib) and weekly Taxol (paclitaxel) (PMID: 26432108). 26432108
ERBB2 amp MET amp esophagus adenocarcinoma sensitive Crizotinib + Lapatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xalkori (crizotinib) and Tykerb (lapatinib) worked synergistically to inhibit growth of an esophageal adenocarcinoma cell line with ERBB2 (HER2) and MET amplification in culture (PMID: 27595477). 27595477
ERBB2 amp MET amp esophageal carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human esophageal carcinoma cell line harboring amplification of ERBB2 (HER2) and MET was resistant to Xalkori (crizotinib) in culture (PMID: 26432108). 26432108
ERBB2 amp MET amp gastric adenocarcinoma resistant AMG 337 Clinical Study Actionable In a clinical case study, a patient with ERBB2 (HER2) and MET amplified gastric adenocarcinoma was insensitive to AMG 337 therapy (PMID: 26432108). 26432108
ERBB2 amp MET amp gastric adenocarcinoma resistant Bevacizumab + Capecitabine + Oxaliplatin + Trastuzumab Clinical Study Actionable In a clinical case study, a patient with ERBB2 (HER2) amplified gastric adenocarcinoma progressed rapidly when treated with Herceptin (trastuzumab) with Xeloda (capecitabine), Eloxatin (oxaliplatin), and Avastin (bevacizumab), and reprofiling of the tumor revealed co-amplification of MET (PMID: 26432108). 26432108
EGFR L858R EGFR T790M MET amp lung adenocarcinoma predicted - sensitive Crizotinib + Osimertinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient with EGFR L858R, EGFR T790M, and MET amplification demonstrated a partial response in her lung lesions and an approximately 90% reduction in the retroperitoneal lymph node and right adrenal gland, and progression-free survival lasting 3 months following treatment with the combination of Tagrisso (osimertinib) and Xalkori (crizotinib) (PMID: 29128427). 29128427
EGFR L858R EGFR T790M MET amp lung adenocarcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR T790M progressed after 19 months on Tagrisso (osimertinib), and was found to have acquired MET amplification (PMID: 29128427). 29128427
EGFR E746_A750del MET amp lung adenocarcinoma sensitive Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) resulted in improved survival in patient-derived xenograft (PDX) models derived from the brain metastasis of a lung adenocarcinoma patient with EGFR E746_A750del (referred to as K745_A750delinsK) and high level MET amplification (PMID: 28961841). 28961841
EGFR E746_A750del MET amp lung adenocarcinoma no benefit Afatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Gilotrif (afatinib) did not demonstrate benefit in patient-derived xenograft (PDX) models derived from the brain metastasis of a lung adenocarcinoma patient with EGFR E746_A750del (referred to as K745_A750delinsK) and high level MET amplification, with all treated mice demonstrating progression (PMID: 28961841). 28961841
EGFR E746_A750del MET amp non-small cell lung carcinoma resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, acquired amplification of MET conferred resistance to Iressa (gefitinib) in a non-small cell lung cancer cell line harboring EGFR E746_A750del in culture (PMID: 27612490). 27612490
EGFR E746_A750del MET amp non-small cell lung carcinoma sensitive CO1686 + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rociletinib (CO-1686) and Xalkori (crizotinib) overcame resistance to Rociletinib (CO-1686) in non-small cell lung cancer cell line harboring EGFR E746_A750del and MET amplification in culture (PMID: 27283993). 27283993
EGFR E746_A750del MET amp lung adenocarcinoma sensitive Afatinib + Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) plus Gilotrif (afatinib) resulted in improved survival with no evidence of tumor 300 days post-transplantation in patient-derived xenograft (PDX) models derived from the brain metastasis of a lung adenocarcinoma patient with EGFR E746_A750del (referred to as K745_A750delinsK) and high level MET amplification (PMID: 28961841). 28961841
EGFR E746_A750del MET amp non-small cell lung carcinoma sensitive Gefitinib + NPS-1034 Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of NPS-1034 to treatment with Iressa (gefitinib) overcame Iressa (gefitinib) resistance in a cell line xenograft model of non-small cell lung cancer reported to harbor EGFR E746_A750del (PMID: 23542356), which has acquired resistance to Iressa (gefitinib) due to MET amplification and over expression, resulting in tumor growth inhibition (PMID: 24165158). 24165158 23542356
EGFR E746_A750del MET amp non-small cell lung carcinoma sensitive Gefitinib + PHA-665752 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PHA-665752 and Iressa (gefitinib) overcame Iressa (gefitinib) resistance in a cell line xenograft model of non-small cell lung cancer reported to harbor EGFR E746_A750del (PMID: 23542356), which has acquired resistance to Iressa (gefitinib) due to MET amplification and over expression, resulting in tumor growth inhibition (PMID: 24165158). 24165158 23542356
EGFR E746_A750del MET amp lung adenocarcinoma resistant Osimertinib Clinical Study Actionable In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EGFR E746_A750del (referred to as K745_A750delinsK) and T790M demonstrated an initial response, but subsequent progression, of the brain metastasis following Tagrisso (osimertinib) treatment, and analysis of the brain metastasis showed loss of EGFR T790M as well as acquisition of high-level MET amplification, and resistance to Tagrisso (osimertinib) was recapitulated in a patient-derived xenograft (PDX) model (PMID: 28961841) 28961841
EGFR E746_A750del MET amp non-small cell lung carcinoma resistant CO1686 Preclinical - Cell line xenograft Actionable In a preclinical study, emergence of MET amplification was associated with resistance to Rociletinib (CO1686) in non-small cell lung cancer cell line xenograft models harboring EGFR E746_A750del (PMID: 27283993). 27283993
MET act mut papillary renal cell carcinoma predicted - sensitive Savolitinib Phase II Actionable In a Phase II trial, treatment with Savolitinib (AZD6094) resulted in an overall response rate (ORR) of 18% (8/44, all partial responses) in the subgroup of patients with MET-driven papillary renal cell carcinoma (PRCC), which included patients with MET kinase domain mutations, compared to an ORR of 0% (0/46) in patients with MET-independent PRCC (PMID: 28644771; NCT02127710). 28644771
MET act mut sarcoma sensitive BMS-777607 Preclinical Actionable In a preclinical study, BMS-777607 (ASLAN002) demonstrated efficacy in blocking Met phosphorylation and inhibiting cell proliferation and metastasis in cultured cells and murine models with activating Met mutations (PMID: 22286523). 22286523
MET act mut Advanced Solid Tumor sensitive Altiratinib Preclinical - Cell culture Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited MET activity, including MET activating mutations, and inhibited proliferation of MET-driven tumor cell lines in culture (PMID: 26285778). 26285778
MET act mut malignant glioma sensitive Merestinib Preclinical - Cell line xenograft Actionable In a preclinical study, Merestinib (LY2801653) demonstrated anti-tumor activity in cell line xenograft models of glioma with autocrine activation of Met signaling (PMID: 23275061). 23275061
MET act mut hepatocellular carcinoma sensitive Tepotinib Preclinical Actionable In a preclinical study, Tepotinib (MSC2156119J) inhibited tumor growth in hepatocellular cancer (HCC) mouse xenograft models with MET overexpression or activation (Cancer Res April 15, 2013; 73(8 Supplement): 925) detail...
MET act mut non-small cell lung carcinoma predicted - sensitive Crizotinib Phase I Actionable In a Phase I clinical trial, Xalkori (crizotinib) was generally well-tolerated and demonstrated preliminary efficacy in patients with non-small cell lung cancer harboring MET exon 14 alterations, with anti-tumor activity demonstrated in 10/15 evaluable patients (J Clin Oncol 34, 2016 (suppl; abstr 108)). detail...
MET act mut Advanced Solid Tumor sensitive Glesatinib Preclinical Actionable In a preclinical study, cells harboring MET activating mutations demonstrated sensitivity to treatment with Glesatinib (MGCD265) in cell-based assays (AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3609). detail...
MET act mut Advanced Solid Tumor sensitive Emibetuzumab Preclinical Actionable In a preclinical study, Emibetuzumab (LY2875358) treatment inhibited MET activation and proliferation of tumor cells with constitutive MET activation in culture, and inhibited tumor growth in xenograft models (PMID: 25231402). 25231402
MET act mut stomach carcinoma sensitive S-49076 Preclinical - Cell line xenograft Actionable In a preclinical study, S-49076 inhibited Met activation, resulting in growth inhibition of gastric carcinoma cells harboring MET activating mutations in culture and in cell line xenograft models (PMID: 23804704). 23804704
EGFR exon 19 del MET act mut lung adenocarcinoma predicted - resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transposon insertions in MET, leading to increased phosphorylation of Met, were associated with resistance to Tagrisso (osimertinib) in a lung adenocarcinoma cell line harboring an EGFR exon 19 deletion in culture (PMID: 29875142). 29875142
EGFR exon 19 del MET act mut lung adenocarcinoma predicted - resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transposon insertions in MET, leading to increased phosphorylation of Met, were associated with resistance to Gilotrif (afatinib) in a lung adenocarcinoma cell line harboring an EGFR exon 19 deletion in culture (PMID: 29875142). 29875142
EGFR exon 19 del MET act mut lung adenocarcinoma predicted - sensitive Osimertinib + Saracatinib Preclinical - Cell culture Actionable In a preclinical study, a lung adenocarcinoma cell line harboring an EGFR exon 19 deletion and with transposon insertions in YES1, leading to increased expression and phosphorylation of Yes1, demonstrated sensitivity to the combination of Tagrisso (osimertinib) and Saracatinib (AZD0530) in culture, resulting in decreased Akt and Erk phosphorylation and reduced cell viability (PMID: 29875142). 29875142
EGFR exon 19 del MET act mut lung adenocarcinoma predicted - sensitive Afatinib + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a lung adenocarcinoma cell line harboring an EGFR exon 19 deletion and with transposon insertions in MET, leading to increased Met phosphorylation, demonstrated sensitivity to the combination of Gilotrif (afatinib) and Xalkori (crizotinib) in culture, resulting in decreased Akt and Erk phosphorylation and reduced cell viability (PMID: 29875142). 29875142
EGFR exon 19 del MET act mut lung adenocarcinoma predicted - resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transposon insertions in MET, leading to increased expression and phosphorylation of Met, were associated with resistance to Tarceva (erlotinib) in a lung adenocarcinoma cell line harboring an EGFR exon 19 deletion in culture (PMID: 29875142). 29875142