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Gene | ALK |
Variant | I1171N |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK I1171N lies within the protein kinase domain of the Alk protein (UniProt.org). I1171N results in increased ligand-independent Alk phosphorylation and activation of the Stat pathway in culture (PMID: 23239810, PMID: 21838707), activation in in vitro assays (PMID: 33674381, PMID: 25517749), is transforming in cell culture (PMID: 23239810, (PMID: 33674381, PMID: 25517749), and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 27565911). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK I1171N ALK mutant ALK I1171X ALK I1171N |
Transcript | NM_004304.5 |
gDNA | chr2:g.29222347A>T |
cDNA | c.3512T>A |
Protein | p.I1171N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29222347A>T | c.3512T>A | p.I1171N | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29222347A>T | c.3512T>A | p.I1171N | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29222347A>T | c.3512T>A | p.I1171N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK I1171N | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | 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 I1171N in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798). | 25393798 |
EML4 - ALK ALK I1171N | lung non-small cell carcinoma | predicted - resistant | Alectinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Alecensa (alectinib) failed to inhibit growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and did not induce tumor regression or reduce Alk phosphorylation in xenograft models (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | 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 in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | lung non-small cell carcinoma | sensitive | Gilteritinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and induced tumor regression and suppressed Alk phosphorylation and downstream signaling in xenograft models (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | lung non-small cell carcinoma | resistant | Entrectinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Iruplinalkib | Preclinical - Cell culture | Actionable | In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | resistant | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Augtyro (repotrectinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK I1171N was identified in post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20), who previously responded to Alecensa (alectinib) (PMID: 36864442). | 36864442 |
EML4 - ALK ALK I1171N | lung adenocarcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a decrease in the liver lesions after 20 days of treatment in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 36864442). | 36864442 |
EML4 - ALK ALK I1171N | inflammatory myofibroblastic tumor | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK I1171N was identified on post-progression biopsy in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK, who previously responded to Alecensa (alectinib) (PMID: 37255276). | 37255276 |
EML4 - ALK ALK I1171N | inflammatory myofibroblastic tumor | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in near resolution of the pleural effusion and decrease in pleural mass in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK and ALK I1171N (PMID: 37255276). | 37255276 |
EML4 - ALK ALK I1171N | pulmonary neuroendocrine tumor | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK I1171N was identified in post-progression biopsy in a patient with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20) who previously responded to Alecensa (alectinib) treatment (PMID: 35832448). | 35832448 |
EML4 - ALK ALK I1171N | pulmonary neuroendocrine tumor | predicted - sensitive | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, Zykadia (ceritinib) treatment resulted in response after 1 month of treatment with tumor shrinkage in a patient with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 35832448). | 35832448 |
ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911). | 27565911 |
ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK I1171N was identified in 6% (3/52) of patients with non-small cell lung cancer harboring an ALK rearrangement after disease progression on first-line Alecensa (alectinib) treatment (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304). | 29935304 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534). | 29650534 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK G1269A | 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 G1269A in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK G1269A | 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 I1171N and G1269A in culture (PMID: 33627640). | 33627640 |
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 |
ALK rearrange ALK I1171N ALK D1203N | 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 I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N ALK L1256F | 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 L1256F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | 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 I1171N and L1256F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | sensitive | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | sensitive | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | 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 F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | predicted - resistant | Alectinib | Preclinical - Pdx | Actionable | In a preclinical study, Alecensa (alectinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | sensitive | Gilteritinib | Preclinical - Pdx | Actionable | In a preclinical study, Xospata (gilteritinib) induced complete tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I, and also induced tumor regression when administered to separate PDX tumors which had demonstrated resistance to Alecensa (alectinib) or Lorbrena (lorlatinib) treatment (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | predicted - resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1198H | 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 L1198H in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | 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 F1174L in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | 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 I1171N and F1174L in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). | 33627640 |
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 |
EML4 - ALK ALK I1171N ALK L1196M | 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 L1196M in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | 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 I1171N and L1196M in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N ALK L1196M | malignant pleural mesothelioma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M and ALK I1171N were identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK who previously responded to Alecensa (alectinib) treatment (PMID: 32600123). | 32600123 |
EML4 - ALK ALK I1171N ALK L1196M | malignant pleural mesothelioma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor regression and a partial response lasting 3.6 months in a patient with malignant pleural mesothelioma harboring EML4-ALK, ALK L1196M, and ALK I1171N (PMID: 32600123). | 32600123 |
EML4 - ALK ALK I1171N ALK V1180L | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK, as well as IDH1 R132H, developed progressive disease after initial response to Alecensa (alectinib), and ALK I1171N and ALK V1180L were identified in the post-progression biopsy along with germline BRCA2 F2801fs (PMID: 35324529). | 35324529 |
EML4 - ALK ALK I1171N ALK L1196M ALK G1202R | malignant pleural mesothelioma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK with ALK L1196M and ALK I1171N who previously responded to Lorbrena (lorlatinib) treatment (PMID: 32600123). | 32600123 |
EML4 - ALK ALK I1171N ALK D1203N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK I1171N ALK D1203N | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Alecensa (alectinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK I1171N ALK D1203N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK E1129V ALK I1171N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK E1129V ALK I1171N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK E1129V ALK I1171N | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK E1129V ALK I1171N | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK C1156Y ALK I1171N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK C1156Y ALK I1171N | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK C1156Y ALK I1171N | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Alecensa (alectinib) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK C1156Y ALK I1171N | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to TPX-0131 in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK C1156Y ALK I1171N | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) treatment inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N and C1156Y in culture (PMID: 36201110). | 36201110 |
ALK I1171N ALK pos | diffuse large B-cell lymphoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an ongoing complete metabolic response 20 months post-transplant in a patient with an ALK-positive large B-cell lymphoma harboring ALK I1171N (PMID: 36809056). | 36809056 |
EML4 - ALK ALK I1171N ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a lung adenocarcinoma patient harboring EML4-ALK with ALK I1171N and G1202R, along with ALK-ENC1 (PMID: 37007089). | 37007089 |