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ALK I1171T - Gene Variant Detail

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Gene ALK
Variant I1171T
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions ALK I1171T lies within the protein kinase domain of the Alk protein (UniProt.org). I1171T confers a gain of function on the Alk protein as indicated by ligand-independent autophosphorylation, activation of Erk1/2, and cell transformation (PMID: 29907598), and has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859).
Associated Drug Resistance Y
Category Variants Paths

ALK mutant ALK act mut ALK I1171T

ALK mutant ALK I1171X ALK I1171T

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Transcript NM_004304.5
gDNA chr2:g.29222347A>G
cDNA c.3512T>C
Protein p.I1171T
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304.4 chr2:g.29222347A>G c.3512T>C p.I1171T RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29222347A>G c.3512T>C p.I1171T RefSeq GRCh38/hg38
NM_004304 chr2:g.29222347A>G c.3512T>C p.I1171T RefSeq GRCh38/hg38

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  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
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  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T 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 I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T 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 I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798). 25393798
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171T in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T 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 I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 34845836). 34845836
EML4 - ALK ALK I1171T 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 I1171T in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive APG-2449 Preclinical - Cell culture Actionable In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35820889). 35820889
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive NVL-655 Preclinical - Cell culture Actionable In a preclinical study, NVL-655 moderately inhibited viability of cells expressing EML4-ALK and ALK I1171T in culture (PMID: 39269178). 39269178
ALK rearrange ALK I1171T lung adenocarcinoma resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T lung adenocarcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534). 25228534
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304). 29935304
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). 29935304
ALK rearrange ALK I1171T lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical study, ALK I1171T was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). detail...
EML4 - ALK ALK C1156Y ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171T ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171T ALK G1269A lung non-small cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response lasting at least 7.4 months in a patient with advanced non-small cell lung cancer harboring EML4-ALK, ALK G1269A, and ALK I1171T who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936). 36096442
ALK I1171T ALK pos lung non-small cell carcinoma predicted - sensitive Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensacove (ensartinib) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569). 31628085
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A were identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20), who previously responded to Xalkori (crizotinib) treatment (PMID: 36093526). 36093526
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A lung adenocarcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 10 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A (PMID: 36093526). 36093526
EML4 - ALK ALK I1171T ALK F1174V lung non-small cell carcinoma predicted - sensitive Ceritinib Case Reports/Case Series Actionable In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring EML4-ALK (e13:e20), ALK F1174V, and ALK I1171T (PMID: 34890832; NCT01283516). 34890832
EML4 - ALK ALK I1171T ALK F1174L ALK L1196M ALK D1203N ALK E1210K ALK G1269A lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M, D1203N, and I1171T were identified at the time of progression on Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). 35123209
ALK I1171T ALK R1192P ALK L1196M ALK F1245V neuroblastoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a neuroblastoma patient harboring ALK F1245V developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired additional ALK variants, I1171T, R1192P, and L1196M, via circulating tumor DNA (PMID: 37147298; NCT03107988). 37147298
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