1. Evaluation of Pan-RAF Inhibitor LY3009120 on Human Uveal Melanoma Cell Line 92-1.
- Author
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Gao YU, Wendt S, Krohn S, Alammar M, Junghanss C, Nolte I, and Escobar HM
- Subjects
- Humans, Cell Line, Tumor, Protein Kinase Inhibitors pharmacology, Mutation, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Cell Survival drug effects, Antineoplastic Agents pharmacology, Phenylurea Compounds pharmacology, Pyrimidines, Uveal Melanoma, Uveal Neoplasms drug therapy, Uveal Neoplasms pathology, Uveal Neoplasms genetics, Melanoma drug therapy, Melanoma pathology, Melanoma genetics, Melanoma metabolism, Cell Proliferation drug effects, Apoptosis drug effects
- Abstract
Background/aim: Uveal melanoma (UM) represents a prevailing primary intraocular malignancy, with a limited median overall survival among metastatic patients, and most tumors lack RAF/RAS mutations. The pan-RAF inhibitor LY3009120 has demonstrated valuable anti-tumor effects in a wide range of RAF/RASmut and wild-type (WT) tumor models. This study aimed to evaluate the antitumor effect of LY3009120 on 92-1 UM cell line., Materials and Methods: The effect of the pan-RAF inhibitor LY3009120 on cell proliferation, metabolic activity, biomass, early and late apoptosis/necrosis, and morphology was characterized in vitro (0.1-5 μM for 48 h/72 h). Furthermore, targeted panel sequencing was used to characterize the mutational landscape of the human 92-1 UM cell line., Results: LY3009120 showed a significant concentration-dependent anti-proliferative effect on 92-1 cells. Cell proliferation and viability were significantly reduced at the lowest effective concentration of 0.5 μM (at 48 and 72 h, p<0.001). Furthermore, LY3009120 caused significant early apoptosis and late apoptosis/necrosis in 92-1 cells at 5 μM. Except for TP53, NGS showed that all 49 additional analysed genes (Oncomine myeloid panel) of 92-1 were wild-type, including BRAF, NRAS, and KRAS., Conclusion: The pan-RAF inhibitor LY3009120 demonstrated a significant anti-tumor effect on human UM cell line 92-1 independent of the molecular BRAF and RAS mutational status., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2024
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