Valproic acid improves the efficacy of oxaliplatin/fluoropyrimidine-based chemotherapy by targeting cancer stem cell via β-Catenin modulation in colorectal cancer.

ABSTRACT: Despite advances in systemic therapeutic approaches, metastatic colorectal cancer (mCRC) patients harboring BRAF or RAS mutations have poor outcomes. Cancer stem cells (CSCs) play central roles in drug resistance and CRC recurrence. Therefore, targeting the epigenetic mechanisms that sustain CSC properties is a promising therapeutic approach. In this study, we report the efficacy of a treatment strategy with the potential to overcome chemotherapy resistance that involves administering the well-known antiepileptic drug and epigenetic agent valproic acid (VPA) and the standard chemotherapy regimen of oxaliplatin/fluoropyrimidine to wild-type CSCs and CSCs with BRAF and RAS mutations in enriched primary spheroid cultures. Notably, we demonstrated that VPA plus chemotherapy was more effective

SUBMITTER: Roca MS 

PROVIDER: S-EPMC12316941 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature