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Molecular Profile ALK F1174L
Therapy Lorlatinib
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 Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). 30322862
ALK F1174L neuroblastoma conflicting Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L neuroblastoma conflicting Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting 13 mo in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1147L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658). 34210658
PubMed Id Reference Title Details
(26554404) The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Full reference...
(30322862) Lorlatinib Treatment Elicits Multiple On- and Off-Target Mechanisms of Resistance in ALK-Driven Cancer. Full reference...
(34210658) Exceptional response to the ALK and ROS1 inhibitor lorlatinib and subsequent mechanism of resistance in relapsed ALK F1174L-mutated neuroblastoma. Full reference...