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Molecular Profile ALK F1174L
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 F1174L neuroblastoma conflicting Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L neuroblastoma conflicting Crizotinib Case Reports/Case Series Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in stable disease lasting 19 months in a patient with advanced neuroblastoma harboring ALK F1174L (PMID: 29352732; NCT00939770). 29352732
ALK F1174L 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, although all 3 patients harboring ALK F1174L had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). 33568345
ALK F1174L neuroblastoma conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of neuroblastoma cell lines harboring ALK F1174L in culture (PMID: 38032104). 38032104
PubMed Id Reference Title Details
(26554404) The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Full reference...
(33568345) Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Full reference...
(29352732) Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. Full reference...
(38032104) SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. Full reference...