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Molecular Profile ALK R1275Q
Therapy Crizotinib
Indication/Tumor Type neuroblastoma
Response Type conflicting

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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...