Driver Gene Mutations and Epigenetics in Colorectal Cancer

Objective: The majority of patients with colorectal cancer are diagnosed with locally advanced and/or disseminated disease, and treatment options include surgery in combination with cytotoxic chemotherapy regimens, biologics, and/or radiotherapy. Thus, colorectal cancer remains a heavy burden on society and health care systems. Mounting evidence show that driver gene mutations play only part of the role in carcinogenesis. Epigenetics are strongly implicated in initiation and progression of colorectal cancer along with major players such as intestinal microbiotic dysbiosis and chronic mucosal inflammation. To assess phenotypic changes in proteins and gene expression, multigene expression signatures based on sequencing techniques have been developed to hopefully improve predictors of the tumor profile, immune response, and therapeutic outcomes. Our objective was to review current advances in the field and to update surgeons and academics on driver gene mutations and epigenetics in colorectal cancer. Background and methods: This is a narrative review studying relevant research published in the PUBMED database from 2012-2018. Results and conclusion: Increased understanding of the molecular biology will improve options to characterize colorectal cancer with regard to mutations and molecular pathways, including microsatellite instability, epigenetics, microbiota, and microenvironment. Research will inevitably improve risk group stratification and targeted treatment approaches. Epigenetic profiling and epigenetic modulating drugs will increase risk stratification, increase accessibility for DNA targeting chemotherapeutics and reduce cytotoxic drug resistance. New generation antibiotics such as biofilm inhibitors and quorum sensing inhibitors are being developed to target the carcinogenetic impact of colonic dysbiosis and inflammation.