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Gene | ALK |
Variant | L1198F |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK L1198F lies within the protein kinase domain of the Alk protein (UniProt.org). L1198F confers a gain of function to the Alk protein as demonstrated by increased Alk kinase activity and downstream Pi3k and Mapk pathway activation (PMID: 21596819). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut ALK L1198F ALK mutant ALK L1198X ALK L1198F |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220759G>A |
cDNA | c.3592C>T |
Protein | p.L1198F |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29220759G>A | c.3592C>T | p.L1198F | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29220759G>A | c.3592C>T | p.L1198F | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29220759G>A | c.3592C>T | p.L1198F | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK rearrange ALK C1156Y ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
EML4 - ALK ALK C1156Y ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F had reduced sensitivity to growth inhibition mediated by Lorbrena (lorlatinib) in comparison to wild-type EML4-ALK in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing EML4-ALK with ALK L1198F was resistant to Zykadia (ceritinib) in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | conflicting | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1198F in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK culture and resulted in only 30% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1198F and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). | 26698910 |
ALK rearrange ALK I1171N ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534). | 29650534 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | predicted - resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | sensitive | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). | 34158340 |
ALK C1156Y ALK L1198F | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK C1156Y and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340). | 34158340 |
ALK L1196M ALK L1198F | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M and ALK L1198F compound mutation in an in vitro assay (PMID: 34158340). | 34158340 |
ALK L1198F ALK G1202R | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK G1202R and L1198F compound mutation in an in vitro assay (PMID: 34158340). | 34158340 |
ALK fusion ALK C1156Y ALK L1198F | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1198F was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK C1156Y who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F was resistant to Lorbrena (lorlatinib) in culture (PMID: 37748191). | 37748191 |
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F | lung non-small cell carcinoma | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F in culture (PMID: 37748191). | 37748191 |
EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F | lung non-small cell carcinoma | sensitive | Afatinib + Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Gilotrif (afatinib) and Xalkori (crizotinib) further inhibited viability of a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F compared to Xalkori (crizotinib) alone in culture (PMID: 37748191). | 37748191 |