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Molecular Profile ALK F1174L
Therapy Lorlatinib
Indication/Tumor Type neuroblastoma
Response Type predicted - sensitive

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK F1174L neuroblastoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease after 4 cycles in a pediatric patient with neuroblastoma harboring ALK F1174L (PMID: 36765519). 36765519
ALK F1174L neuroblastoma predicted - sensitive 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 F1174L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658). 34210658
ALK F1174L neuroblastoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response in 3 of 5 patients and a partial response in 1 of 5 patients with neuroblastoma harboring ALK F1174L (PMID: 37561984). 37561984
ALK F1174L neuroblastoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a minor response with stable disease in a neuroblastoma patient harboring ALK F1174L (PMID: 37147298; NCT03107988). 37147298
ALK F1174L neuroblastoma predicted - sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited downstream signaling, viability, and invasion in neuroblastoma cell lines harboring ALK F1174L in culture, and decreased tumor growth and increased survival in cell line xenograft models (PMID: 38032104). 38032104
ALK F1174L neuroblastoma predicted - sensitive 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 predicted - sensitive Lorlatinib Preclinical Actionable In a preclinical study, Lorbrena (lorlatinib) treatment induced tumor regression in a transgenic mouse model of neuroblastoma harboring ALK F1174L (PMID: 27483357). 27483357
ALK F1174L neuroblastoma predicted - sensitive 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
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...
(37147298) Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Full reference...
(36765519) Therapeutic Targeting of ALK in Neuroblastoma: Experience of Italian Precision Medicine in Pediatric Oncology. Full reference...
(37561984) Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults. Full reference...
(38032104) SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. Full reference...
(27483357) The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN. Full reference...