Chromatin factors: Ready to roll as biomarkers in metastatic colorectal cancer?

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and stands as the fourth leading cause of cancer-related fatalities in 2020. Survival rates for metastatic disease have slightly improved in recent decades, with clinical trials showing median overall survival of approximately 24-30 months. This progress can be attributed to the integration of chemotherapeutic treatments alongside targeted therapies and immunotherapy. Despite these modest improvements, the primary obstacle to successful treatment for advanced CRC lies in the development of chemoresistance, whether inherent or acquired, which remains the major cause of treatment failure. Epigenetics has emerged as a hallmark of cancer, contributing to master transcription regulation and genome stability maintenance. As a result, epigenetic factors are starting to appear as potential clinical biomarkers for diagnosis, prognosis, and prediction of treatment response in CRC.In recent years, numerous studies have investigated the influence of DNA methylation, histone modifications, and chromatin remodelers on responses to chemotherapeutic treatments. While there is accumulating evidence indicating their significant involvement in various types of cancers, the exact relationship between chromatin landscapes and treatment modulation in CRC remains elusive. This review aims to provide a comprehensive summary of the most pertinent and extensively researched epigenetic-associated mechanisms described between 2015 and 2022 and their potential usefulness as predictive biomarkers in the metastatic disease.