Mismatch Repair and Colon Cancer: Mechanisms and Therapies Explored

• Published in: Trends in molecular medicine Vol. 22; no. 4; pp. 274 - 289
• Main Authors: Li, Stephen K.H, Martin, Alberto
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2016
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biomarkers; Butyrates - metabolism; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - etiology; Colonic Neoplasms - metabolism; Colonic Neoplasms - prevention & control; DNA Mismatch Repair; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Humans; Immunotherapy; inflammation; Inflammation - complications; Inflammation - genetics; Inflammation - metabolism; Lynch syndrome; microbiota; microRNAs; mismatch repair; Molecular Targeted Therapy; Oxidative Stress; Pathology; Programmed Cell Death 1 Receptor - antagonists & inhibitors; microbiota; microRNAs; mismatch repair; inflammation; colon cancer; Lynch syndrome
• ISSN: 1471-4914; 1471-499X
• DOI: 10.1016/j.molmed.2016.02.003

Colorectal cancer (CRC) remains one of the most prevalent cancers worldwide. In sporadic CRC, mutations frequently occur in the DNA mismatch repair (MMR) pathway. In addition, germline MMR mutations have been linked to Lynch syndrome, the most common form of hereditary CRC. Although genetic mutations, diet, inflammation, and the gut microbiota can influence CRC, it is unclear how MMR deficiency relates to these factors to modulate disease. In this review, the association of MMR to the etiology of CRC is examined, particularly in the context of microRNAs (miRNAs), inflammation, and the microbiome. We also discuss the most current targeted therapies, methods of prevention, and molecular biomarkers against MMR-deficient CRC, all of which are encouraging advancements in the field.