# Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer

## TL;DR

This review explores how inflammation and epigenetic changes contribute to the progression and treatment resistance of high-grade serous ovarian cancer.

## Contribution

The paper provides a comprehensive analysis of the interplay between inflammatory pathways and epigenetic alterations in HGSOC.

## Key findings

- Chronic inflammation in the tumor microenvironment promotes tumor growth, immune suppression, and metastasis.
- Epigenetic mechanisms like DNA methylation and histone modifications contribute to treatment resistance in HGSOC.
- Combining anti-inflammatory drugs with epigenetic therapies shows promise in overcoming resistance.

## Abstract

High-grade serous ovarian cancer (HGSOC) is often diagnosed at advanced stages (III/IV), with approximately 80% of patients experiencing relapse due to therapeutic resistance. The disease progression is largely influenced by a dynamic tumor microenvironment (TME), which is marked by sustained inflammation, immune evasion, and epigenetic reprogramming. This review investigates the dual role of inflammatory pathways and epigenetic alterations in driving HGSOC progression and chemo-resistance. A comprehensive literature search of articles from 2000 to 2025 was conducted across PubMed, Google Scholar, and Research Rabbit using search terms including “HGSOC,” “epigenetics,” “inflammation,” and “chemoresistance.” Of 1,166 identified publications, 593 peer-reviewed studies comprising original research, clinical trials, meta-analyses, and reviews were critically analyzed. Findings reveal that chronic inflammation in the TME enhances tumor proliferation, immune suppression, epithelial-mesenchymal transition, and metastasis through cytokines, interferons, and chemokines. Epigenetic mechanisms such as DNA methylation, histone modifications, miRNA and lncRNA contribute to tumor plasticity and treatment failure. Emerging therapies, including histone deacetylase inhibitors, DNA methyltransferase inhibitors, and immune checkpoint inhibitors, anti-inflammatory drugs demonstrate potential in overcoming resistance when used in combination. Integrative treatment strategies that target both inflammatory signaling and epigenetic dysregulation offer a promising avenue for improving patient outcomes. Further clinical exploration of such combination therapies is warranted to address the urgent need for effective interventions in HGSOC.