Molecular Profile Detail

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Profile Name ALK amp
Gene Variant Detail

ALK amp (no effect)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK amp TP53 wild-type neuroblastoma sensitive Crizotinib + Cyclophosphamide + Topotecan Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). 26438783
ALK rearrange ALK amp lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a retrospective analysis, two non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK amplification (PMID: 25724526). 25724526
ALK rearrange ALK amp lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, three patients with non-small cell lung carcinoma co-harboring an ALK rearrangement and ALK amplification demonstrated resistance to Xalkori (crizotinib) treatment (PMID: 27432227). 27432227
ALK F1174V ALK amp neuroblastoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK F1174L ALK amp neuroblastoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK F1174V ALK amp neuroblastoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). 29907598
ALK F1174L ALK amp neuroblastoma sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174L in culture (PMID: 29907598). 29907598
ALK amp ALK pos lung non-small cell carcinoma predicted - sensitive Ensartinib Case Reports/Case Series Actionable In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 56% (5/9, all partial responses) and stable disease in 44% (4/9) of patients with ALK-positive non-small cell lung cancer with ALK amplification (PMID: 31628085; NCT0321569). 31628085
ALK rearrange ALK amp lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical study, ALK amplification was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on first-line Alecensa (alectinib) treatment and in 4% (2/56) of patients after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). detail...
ALK F1174V ALK amp neuroblastoma sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Augtyro (repotrectinib) inhibited downstream signaling and proliferation, and induced apoptosis in a neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 31852910). 31852910
ALK amp TP53 wild-type neuroblastoma sensitive Idasanutlin + Lorlatinib Preclinical - Pdx Actionable In a preclinical study, combination treatment with Lorbrena (lorlatinib) and Idasanutlin (RG7388) resulted in an additive effect on tumor growth inhibition with complete remission in a patient-derived xenograft (PDX) model of TP53 wild-type neuroblastoma with ALK amplification and overexpression (PMID: 36602782). 36602782
ALK F1174V ALK amp TP53 wild-type neuroblastoma sensitive Idasanutlin + TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). 36602782
ALK amp TP53 wild-type neuroblastoma sensitive Alectinib + Idasanutlin Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line with ALK amplification in culture (PMID: 36602782). 36602782
ALK F1174V ALK amp TP53 wild-type neuroblastoma sensitive Alectinib + Idasanutlin Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). 36602782
ALK F1174L ALK G1202R ALK D1203N ALK amp neuroblastoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK amplification, and ALK G1202R and D1203N each in cis with F1174L via circulating tumor DNA (PMID: 37147298; NCT03107988). 37147298
ALK del exon2 ALK del exon3 ALK amp neuroblastoma sensitive Ceritinib + Ribociclib Preclinical - Cell culture Actionable In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) inhibited proliferation in a neuroblastoma cell line harboring a deletion of ALK exons 2 and 3 and ALK amplification in culture (PMID: 27986745). 27986745
ALK amp TP53 wild-type neuroblastoma sensitive Ceritinib + CGM097 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type, ALK-amplified neuroblastoma cell line in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). 28425916