# Chemoresistance

In KRAS-mutant and KRAS wild-type pancreatic ductal adenocarcinoma cells (PANC-1, BxPC-3) and a PANC-1 subcutaneous xenograft model, this study shows that the natural polyphenol ellagic acid (EA) combined with the GPX4 inhibitor RSL3 synergistically reduces cell viability and suppresses tumor growth by activating p38 MAPK and upregulating Keap1 to inhibit the Nrf2/HO-1 antioxidant axis, amplifying ferroptotic hallmarks such as iron accumulation, lipid peroxidation, and GPX4 downregulation, with Fer-1 rescuing viability while apoptosis, necroptosis, and autophagy inhibitors do not.

In KRAS-mutant and KRAS wild-type pancreatic ductal adenocarcinoma cells (PANC-1, BxPC-3) and a PANC-1 subcutaneous xenograft model, this study shows that the natural polyphenol ellagic acid (EA) combined with the GPX4 inhibitor RSL3 synergistically reduces cell viability and suppresses tumor growth by activating p38 MAPK and upregulating Keap1 to inhibit the Nrf2/HO-1 antioxidant axis, amplifying ferroptotic hallmarks such as iron accumulation, lipid peroxidation, and GPX4 downregulation, with Fer-1 rescuing viability while apoptosis, necroptosis, and autophagy inhibitors do not.

This review systematically examines how DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA networks drive chemoresistance and recurrence in ovarian cancer, summarizes clinical trial results of epigenetic agents (DNMT, HDAC, and EZH2 inhibitors) combined with PARP inhibitors or immunotherapy, and reviews biomarker advances based on circulating cfDNA methylation, circulating miRNAs, and AI-based liquid biopsy platforms, proposing a precision oncology framework for patient stratification and real-time monitoring of chemoresistance.

This review systematically examines how DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA networks drive chemoresistance and recurrence in ovarian cancer, summarizes clinical trial results of epigenetic agents (DNMT, HDAC, and EZH2 inhibitors) combined with PARP inhibitors or immunotherapy, and reviews biomarker advances based on circulating cfDNA methylation, circulating miRNAs, and AI-based liquid biopsy platforms, proposing a precision oncology framework for patient stratification and real-time monitoring of chemoresistance.