Therapeutic Targeting of ALK in Neuroblastoma: Experience of Italian Precision Medicine in Pediatric Oncology.

Autor: Pastorino F; UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Capasso M; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy.; CEINGE Biotecnologie Avanzate, Via G. Salvatore, 486, 80145 Napoli, Italy., Brignole C; UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Lasorsa VA; CEINGE Biotecnologie Avanzate, Via G. Salvatore, 486, 80145 Napoli, Italy., Bensa V; UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Perri P; UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Cantalupo S; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy.; CEINGE Biotecnologie Avanzate, Via G. Salvatore, 486, 80145 Napoli, Italy., Giglio S; UO Pediatria-Neonatologia/Nido PO A. Ajello ASP Trapani, 91100 Trapani, Italy., Provenzi M; Pediatric Oncology, Ospedale Papa Giovanni XXIII, Piazza Organizzazione Mondiale Sanità 1, 24127 Bergamo, Italy., Rabusin M; Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/1, 34137 Trieste, Italy., Pota E; UOSD di Ematologia ed Oncologia Pediatrica, Università Degli Studi Della Campania 'Luigi Vanvitelli,' Piazza Luigi Miraglia 2, 80138 Napoli, Italy., Cellini M; Division of Paediatric Hemato-Oncology, University Hospital Azienda Policlinico di Modena, Via del Pozzo 71, 41124 Modena, Italy., Tondo A; Department of Hematology-Oncology, Anna Meyer Children's Hospital, VialePieraccini 24, 50139 Firenze, Italy., De Ioris MA; Department of Paediatric Haematology/Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Sementa AR; Dipartimento di Patologia, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Garaventa A; UOC Oncologia, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy., Ponzoni M; UOSD Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Amoroso L; UOC Oncologia, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genova, Italy.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Jan 17; Vol. 15 (3). Date of Electronic Publication: 2023 Jan 17.
DOI: 10.3390/cancers15030560
Abstrakt: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the ALK (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment. Our goal, within the Italian project of PeRsonalizEdMEdicine (PREME), was to evaluate the genomic status of patients with relapsed/refractory NB and to implement targeted therapies in those with targetable mutations. From November 2018 to November 2021, we performed Whole Exome Sequencing or Targeted Gene Panel Sequencing in relapsed/refractory NB patients in order to identify druggable variants. Activating mutations of ALK were identified in 8(28.57%) of 28 relapsed/refractory NB patients. The mutation p.F1174L was found in six patients, whereas p.R1275Q was found in one and the unknown mutation p.S104R in another. Three patients died before treatment could be started, while five patients received crizotinib: two in monotherapy (one with p.F1174L and the other with p.S104R) and three (with p.F1174L variant) in combination with chemotherapy. All treated patients showed a clinical improvement, and one had complete remission after two cycles of combined treatment. The most common treatment-related toxicities were hematological. ALK inhibitors may play an important role in the treatment of ALK-mutated NB patients.
Databáze: MEDLINE
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