Epigenetics of colorectal cancer: biomarker and therapeutic potential

By G. Jung, E. Hernández-Illán, L. Moreira, F. Balaguer, A. Goel. Nature reviews: Gastroenterology & hepatology, 2020

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Colorectal cancer (CRC), a leading cause of cancer-related death worldwide, evolves as a result of the stepwise accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium, leading to the development of colorectal adenomas and invasive adenocarcinomas. Although genetic alterations have a major role in a subset of CRCs, the pathophysiological contribution of epigenetic aberrations in this malignancy has attracted considerable attention. Data from the past couple of decades has unequivocally illustrated that epigenetic marks are important molecular hallmarks of cancer, as they occur very early in disease pathogenesis, involve virtually all key cancer-associated pathways and, most importantly, can be exploited as clinically relevant disease biomarkers for diagnosis, prognostication and prediction of treatment response. In this Review, we summarize the current knowledge on the best-studied epigenetic modifications in CRC, including DNA methylation and histone modifications, as well as the role of non-coding RNAs as epigenetic regulators. We focus on the emerging potential for the bench-to-bedside translation of some of these epigenetic alterations into clinical practice and discuss the burgeoning evidence supporting the potential of emerging epigenetic therapies in CRC as we usher in the era of precision medicine. Epigenetic modifications and regulators, including DNA methylation, histone modifications and non-coding RNA species, have key pathophysiological roles in colorectal cancer (CRC). This Review outlines these epigenetic aberrations in CRC and their potential as diagnostic, prognostic and predictive biomarkers and therapeutic targets. Epigenetic changes, notably DNA methylation and histone modifications, have key pathophysiological roles in the initiation and progression of colorectal cancer (CRC). Non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long ncRNAs are also important regulators of gene expression and are implicated in many CRC-related pathways. Epigenetic changes and altered expression of ncRNAs can be exploited as biomarkers for the diagnosis, prognostication and prediction of treatment response in CRC. Biomarkers based on DNA methylation have been commercialized, and some have already found their way into clinical practice and guidelines in CRC. miRNAs are the most promising and fastest-growing group of potential future biomarkers for CRC; their implications in clinical practice are expected within the next decade. Epigenetic changes are potentially reversible and are attractive targets for future cancer treatments; preclinical and phase I/II studies have proven the utility of epigenetic modifiers.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/29996e580760d3b009d807917cfc95b6e52e091a