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Gene | ALK |
Variant | amp |
Impact List | none |
Protein Effect | no effect |
Gene Variant Descriptions | ALK amplification indicates an increased number of copies of the ALK gene. However, the mechanism causing the increase is unspecified. |
Associated Drug Resistance | |
Category Variants Paths |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK amp | neuroblastoma | no benefit | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although both patients harboring ALK amplification had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). | 33568345 |
ALK amp | neuroblastoma | no benefit | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) was less efficient than Lorlatinib (PF-06463922) to induced growth inhibition in ALK-amplified neuroblastoma cells in culture (PMID: 26554404). | 26554404 |
ALK amp | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 26554404). | 26554404 |
ALK amp | neuroblastoma | sensitive | Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a panel of ALK-amplified neuroblastoma cell lines in culture, and inhibited tumor growth in a patient-derived xenograft (PDX) model (PMID: 36602782). | 36602782 |
ALK amp | lung non-small cell carcinoma | no benefit | Belizatinib | Phase I | Actionable | In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). | 31217479 |
ALK amp | neuroblastoma | predicted - sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK amplification in culture (PMID: 34482287). | 34482287 |
ALK amp | neuroblastoma | sensitive | CEP-28122 | Preclinical - Cell culture | Actionable | In a preclinical study, CEP-28122 inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 22203728). | 22203728 |
ALK amp | neuroblastoma | predicted - sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK amplification in culture (PMID: 34482287). | 34482287 |
ALK amp | neuroblastoma | predicted - sensitive | NVL-655 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-655 inhibited proliferation of neuroblastoma cell lines with ALK amplification in culture (Cancer Res (2022) 82 (12_Supplement): 3337). | detail... |
ALK amp | neuroblastoma | no benefit | Cyclophosphamide + Doxorubicin + Lorlatinib + Vincristine Sulfate | Preclinical - Pdx | Actionable | In a preclinical study, addition of Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Oncovin (vincristine) to Lorbrena (lorlatinib) did not improve tumor growth inhibition in a patient-derived xenograft (PDX) model of neuroblastoma with ALK amplification and overexpression (PMID: 36602782). | 36602782 |