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Molecular Profile	Treatment Approach
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Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
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Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
ALK	E1154K	missense	unknown	ALK E1154K lies within the protein kinase domain of the Alk protein (UniProt.org). E1154K has been identified in the scientific literature (PMID: 31585938, PMID: 38448512), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Feb 2025).
ALK	L1196P	missense	gain of function - predicted	ALK L1196P lies within the protein kinase domain of the Alk protein (UniProt.org). L1196P results in both increased phosphorylation of Alk and proliferation, and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK in culture (PMID: 38448512), and therefore, is predicted to lead to a gain of Alk protein function.	Y
ALK	L1198R	missense	unknown	ALK L1198R lies within the protein kinase domain of the Alk protein (UniProt.org). L1198R has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 38448512), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Mar 2025).	Y
ALK	C1235R	missense	unknown	ALK C1235R lies within the protein kinase domain of the Alk protein (UniProt.org). C1235R has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK compound mutations (PMID: 38448512), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Feb 2025).	Y
ALK	C1237Y	missense	gain of function - predicted	ALK C1237Y lies within the protein kinase domain of the Alk protein (UniProt.org). C1237Y results in both increased phosphorylation of Alk and proliferation, and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK in culture (PMID: 38448512), and therefore, is predicted to lead to a gain of Alk protein function.	Y

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Showing 1 to 25 of 25 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK C1235R ALK C1237Y	lung non-small cell carcinoma	predicted - resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, a patient with relapsed non-small cell lung cancer harboring EML4-ALK developed progressive disease while on treatment with Alunbrig (brigatinib), and was found to have acquired ALK C1235R and ALK C1237Y in trans by liquid biopsy (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Brigatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196M and ALK G1202R were identified in the post-progression circulating tumor DNA of a patient with non-small cell lung cancer harboring EML4-ALK who progressed on treatment with Alunbrig (brigatinib), and in a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512, PMID: 36806896).	36806896 38448512
EML4 - ALK ALK L1196P	lung non-small cell carcinoma	predicted - resistant	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK L1196P was identified in the post-progression circulating tumor DNA of a patient with relapsed non-small cell lung cancer harboring EML4-ALK treated with Lorbrena (lorlatinib), and in a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to TPX-0131 in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK C1237Y	Advanced Solid Tumor	resistant	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Augtyro (repotrectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196M ALK G1202R	Advanced Solid Tumor	resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	TPX-0131	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to TPX-0131 in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Repotrectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Augtyro (repotrectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1196P	Advanced Solid Tumor	resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Alectinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Alecensa (alectinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Brigatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Alunbrig (brigatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Ceritinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Zykadia (ceritinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	Advanced Solid Tumor	predicted - resistant	Lorlatinib	Preclinical - Cell culture	Actionable	In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512).	38448512
EML4 - ALK ALK L1198R	lung non-small cell carcinoma	predicted - resistant	Crizotinib	Preclinical - Cell culture	Actionable	In a clinical case study, ALK L1198R was identified in the post-progression circulating tumor DNA of a patient with relapsed non-small cell lung cancer harboring EML4-ALK treated with Xalkori (crizotinib), and in a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Xalkori (crizotinib) in culture (PMID: 38448512).	38448512

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