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| Molecular Profile | ALK R1275Q |
| Therapy | Crizotinib |
| Indication/Tumor Type | neuroblastoma |
| Response Type | conflicting |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK R1275Q | neuroblastoma | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104). | 38032104 |
| ALK R1275Q | neuroblastoma | conflicting | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment obtained through a Phase I trial resulted in a complete response, with complete and durable remission for 5 years on therapy, in a pediatric patient with hereditary neuroblastoma harboring germline ALK R1275Q (PMID: 40294355). | 40294355 |
| ALK R1275Q | neuroblastoma | conflicting | 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, among the 12 patients harboring ALK R1275Q, 1 achieved a complete response, 2 achieved partial responses, and 2 achieved prolonged stable diseases (PMID: 33568345; NCT00939770). | 33568345 |
| ALK R1275Q | neuroblastoma | conflicting | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK R1275Q in culture, and only delayed tumor growth in cell line xenograft models (PMID: 26554404). | 26554404 |
| ALK R1275Q | neuroblastoma | conflicting | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK R1275Q in culture (PMID: 29907598). | 29907598 |
| ALK R1275Q | neuroblastoma | conflicting | Crizotinib | Preclinical | Actionable | In a preclinical study, Xalkori (crizotinib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913). | 24811913 |
| PubMed Id | Reference Title | Details |
|---|---|---|
| (26554404) | The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. | Full reference... |
| (29907598) | Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib. | Full reference... |
| (33568345) | Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). | Full reference... |
| (24811913) | Activated Alk triggers prolonged neurogenesis and Ret upregulation providing a therapeutic target in ALK-mutated neuroblastoma. | Full reference... |
| (38032104) | SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. | Full reference... |
| (40294355) | Anaplastic Lymphoma Kinase Inhibition Therapy for Hereditary Neuroblastoma. | Full reference... |