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Profile Name | ALK amp |
Gene Variant Detail | |
Relevant Treatment Approaches |
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 |