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Ref Type Journal Article
PMID (33627640)
Authors Mizuta H, Okada K, Araki M, Adachi J, Takemoto A, Kutkowska J, Maruyama K, Yanagitani N, Oh-Hara T, Watanabe K, Tamai K, Friboulet L, Katayama K, Ma B, Sasakura Y, Sagae Y, Kukimoto-Niino M, Shirouzu M, Takagi S, Simizu S, Nishio M, Okuno Y, Fujita N, Katayama R
Title Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer.
Journal Vol Issue Date Pages Journal Short Title
Nature communications 12 1 2021 02 24 1261 Nat Commun
URL
Abstract Text ALK gene rearrangement was observed in 3%-5% of non-small cell lung cancer patients, and multiple ALK-tyrosine kinase inhibitors (TKIs) have been sequentially used. Multiple ALK-TKI resistance mutations have been identified from the patients, and several compound mutations, such as I1171N + F1174I or I1171N + L1198H are resistant to all the approved ALK-TKIs. In this study, we found that gilteritinib has an inhibitory effect on ALK-TKI-resistant single mutants and I1171N compound mutants in vitro and in vivo. Surprisingly, EML4-ALK I1171N + F1174I compound mutant-expressing tumors were not completely shrunk but regrew within a short period of time after alectinib or lorlatinib treatment. However, the relapsed tumor was markedly shrunk after switching to the gilteritinib in vivo model. In addition, gilteritinib was effective against NTRK-rearranged cancers including entrectinib-resistant NTRK1 G667C-mutant and ROS1 fusion-positive cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A 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 G1269A in culture (PMID: 33627640). 33627640
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 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 G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (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 L1196Q 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 L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S 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 L1196Q Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
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 G1269A Advanced Solid Tumor predicted - resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V 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 D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y 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 C1156Y 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 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 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 L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I 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 F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q 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 L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S 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 I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L 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 V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K 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 T1151K in culture (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 I1171S ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to treatment with Rozlytrek (entrectinib) 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 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 F1174V 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 F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q 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 L1196Q 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
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V 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 F1245V in culture (PMID: 33627640). 33627640
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 L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to 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 I1171S 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 I1171S and G1269A 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 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 L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N 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 D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Rozlytrek (entrectinib) 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 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 T1151K 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 T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK 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 L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y 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 C1156Y 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 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 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 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 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 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 L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S 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 I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I 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 F1174I 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 F1245V 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 F1245V 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 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 F1174I 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 F1174I 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 EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK 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 F1174I in culture (PMID: 33627640). 33627640
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 L1196M ALK D1203N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
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 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 L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) 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) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK 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 G1269A 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 AXL over exp lung non-small cell carcinoma resistant Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit cell growth, phosphorylation of Alk and Axl, or downstream signaling in a non-small cell lung cancer cell line harboring EML4-ALK and overexpressing AXL in culture, and did not inhibit tumor growth in cell line xenograft models (PMID: 33627640). 33627640
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 G1202R Advanced Solid Tumor resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I 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 F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K 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 T1151K 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) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F 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 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 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 D1203N 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 D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1245V were resistant to treatment with Rozlytrek (entrectinib) 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 treatment with Xalkori (crizotinib) 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 EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Zykadia (ceritinib) 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 L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK T1151K demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
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 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 G1269A 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 L1196Q Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
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 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 F1245V 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 F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L 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 V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L 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 V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L 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 V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
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 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 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 D1203N ALK F1245V 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 D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L 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 V1180L 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) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK V1180L were resistant to Alecensa (alectinib) 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 Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) in culture (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 C1156Y 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 C1156Y 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 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 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 F1174V 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 F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V 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 F1174V 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 T1151K 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 T1151K 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 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 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 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 D1203N ALK F1245V Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
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 D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L 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 V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK 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 L1256F in culture (PMID: 33627640). 33627640
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 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 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 L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Rozlytrek (entrectinib) 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 I1171S 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 I1171S 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 AXL over exp lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xospata (gilteritinib) inhibited cell growth, phosphorylation of Alk and Axl, and downstream signaling in a non-small cell lung cancer cell line harboring EML4-ALK and overexpressing AXL in culture and suppressed tumor growth in cell line xenograft models and inhibited tumor growth when administered to separate xenograft models that had previously demonstrated resistance to Alecensa (alectinib) treatment (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R 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 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 T1151K 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 T1151K 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 F1245V 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 F1245V in culture (PMID: 33627640). 33627640
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 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 F1174V 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 F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Lorbrena (lorlatinib) 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 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 L1196M ALK G1202R Advanced Solid Tumor resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated resistance to Xalkori (crizotinib) 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 L1196M ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
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 C1156Y 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 C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S 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 I1171S 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 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 D1203N ALK F1245V 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 D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V 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 F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N 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 D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S 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 I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A 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 G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK 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 L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K 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 T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Rozlytrek (entrectinib) 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 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 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 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 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 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 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 G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to 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 I1171S ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N 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 D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor predicted - sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q 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 L1196Q in culture (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 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 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 L1196M ALK D1203N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V 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 F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V 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 F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640