Julie Delyon1,2, Céleste Lebbe1,2, Nicolas Dumaz3. 1. Université de Paris, INSERM U976, Team 1, Human Immunology Pathophysiology & Immunotherapy (HIPI). 2. AP-HP Hôpital Saint Louis, Service de Dermatologie. 3. INSERM, U976, Team 1, Human Immunology Pathophysiology & Immunotherapy (HIPI), Paris, France.
Abstract
PURPOSE OF REVIEW: Melanoma treatment have been revolutionized since 2010 by the development of immune checkpoint inhibitors, and, for BRAF-mutated melanoma, targeted therapies based on BRAF and MEK inhibitors, which is a model of effective targeted therapy in cancer. However, patients with BRAF wild type cannot benefit for such treatments. In this review, we will focus on the current clinical development of targeted therapies beyond BRAF, in NRAS-mutated and KIT-altered melanoma. RECENT FINDINGS: In NRAS-mutated melanoma, targeted therapies based on MEK inhibition are being developed as monotherapy or in combination with MAPK, PI3K or CDK4/6 inhibitor. Targeted therapies of KIT-altered melanoma patients is based in KIT inhibitor (mostly imatinib, nilotinib), although for both melanoma subtypes, results are for now disappointing as compared with BRAF and MEK inhibitors in BRAF-mutated melanoma. SUMMARY: Combined therapeutic targeted strategies are awaited in NRAS-mutated and KIT-altered melanoma and could provide additional benefit.
PURPOSE OF REVIEW: Melanoma treatment have been revolutionized since 2010 by the development of immune checkpoint inhibitors, and, for BRAF-mutated melanoma, targeted therapies based on BRAF and MEK inhibitors, which is a model of effective targeted therapy in cancer. However, patients with BRAF wild type cannot benefit for such treatments. In this review, we will focus on the current clinical development of targeted therapies beyond BRAF, in NRAS-mutated and KIT-altered melanoma. RECENT FINDINGS: In NRAS-mutated melanoma, targeted therapies based on MEK inhibition are being developed as monotherapy or in combination with MAPK, PI3K or CDK4/6 inhibitor. Targeted therapies of KIT-altered melanomapatients is based in KIT inhibitor (mostly imatinib, nilotinib), although for both melanoma subtypes, results are for now disappointing as compared with BRAF and MEK inhibitors in BRAF-mutated melanoma. SUMMARY: Combined therapeutic targeted strategies are awaited in NRAS-mutated and KIT-altered melanoma and could provide additional benefit.
Authors: Kevin Cheung; Aaron D Bossler; Sarah L Mott; Megan Zeisler; Julie McKillip; Yousef Zakharia; Brian L Swick; Jennifer G Powers Journal: Front Oncol Date: 2022-05-30 Impact factor: 5.738
Authors: Alicia Baumgartner; Natalia Stepien; Lisa Mayr; Sibylle Madlener; Christian Dorfer; Maria T Schmook; Tatjana Traub-Weidinger; Daniela Lötsch-Gojo; Dominik Kirchhofer; Dominik Reisinger; Cora Hedrich; Saleha Arshad; Stefan Irschik; Heidrun Boztug; Gernot Engstler; Marie Bernkopf; Fikret Rifatbegovic; Christoph Höller; Irene Slavc; Walter Berger; Leonhard Müllauer; Christine Haberler; Amedeo A Azizi; Andreas Peyrl; Johannes Gojo Journal: J Pers Med Date: 2021-04-12