Cytotoxic and Apoptotic Agent Encorafenib Controversially Alters Invasive Properties of Castration-Resistant Prostate Cancer Cells with High and Moderate Metastatic Potential

Authors : Işıl Ezgi Eryılmaz, Ceyda Colakoglu Bergel, Bilge Arıöz, Ünal Egeli

Pages : 263-270

Doi:10.20515/otd.1598241

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Publication Date : 2025-02-27

Article Type : Research Paper

Abstract :Metastatic castration-resistant prostate cancer (mCRPC) is a highly aggressive form of prostate cancer (PCa) with limited treatment options and poor prognosis. BRAF mutations, although rare, contribute to the progression of PCa by activating the MAPK signaling pathway, which is implicated in cellular proliferation, survival, and metastasis. In this study, we first investigated the potential anticancer and anti-invasive effects of Encorafenib (Enco), a second-generation BRAF inhibitor, in mCRPC cell lines with varying metastatic potentials: moderate metastatic DU145 (BRAF-mutated) and high metastatic PC3 (PTEN-null). Our results showed that Enco reduced cell viability and induced apoptosis in both cell lines in a concentration- and time-dependent manner, with DU145 cells being more sensitive. While Enco inhibited migration in PC3 cells, it had no significant effect on the migration of DU145 cells. Furthermore, Enco treatment increased the expression of genes related to angiogenesis and invasion (VEGF-a, HIF1-a, MMP9, and MMP2) in both cell lines. These findings suggest that while Enco may have potential as a cytotoxic agent for mCRPC, its effects on migration, invasion, and gene expression may vary based on the specific genetic alterations of the cancer cells. This highlights the need for personalized treatment strategies and the potential for adaptive resistance mechanisms. Further studies, particularly combination therapies targeting multiple signaling pathways, are necessary to improve the therapeutic efficacy of Enco in mCRPC.
Keywords : Metastatik kastrasyona-dirençli prostat kanseri, Encorafenib, BRAF, PTEN, migrasyon, invazyon