Targeting RAF1 gene fusions with MEK inhibition in metastatic melanoma.

Autor: Khaddour K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States., Haq R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States., Buchbinder EI; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States., Liu D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States., Manos MP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States., Ott PA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States., Hodi FS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States., Insco ML; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA 02115, United States.; Harvard Medical School, Boston, MA 02115, United States.
Jazyk: angličtina
Zdroj: The oncologist [Oncologist] 2024 Nov 06. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1093/oncolo/oyae297
Abstrakt: The biological and clinical relevance of gene fusions in melanoma is unknown. Reports and preclinical data have suggested that tumor cells with specific rearrangements such as RAF1 gene fusions could be therapeutically targeted. To investigate the relevance of targeted therapy in patients with melanoma harboring RAF1 gene fusions, we reviewed records of 1268 melanoma patients with targeted sequencing data at the Dana-Farber Cancer Institute. We identified 9 cases and report here on their clinicopathologic characteristics. We describe the favorable outcome of 2 patients who received MEK inhibitor therapy, including 1 patient with a durable response. We coalesced our data with published reports of patients with RAF1 gene fusions who were treated with targeted therapy. We find that single-agent MEK inhibition has anti-tumor activity in melanoma patients harboring an RAF1 gene fusion, and we propose that patients with RAF1 gene fusions should be considered for single-agent MEK inhibitor therapy.
(© The Author(s) 2024. Published by Oxford University Press.)
Databáze: MEDLINE