Pharmacogenomics in colorectal cancer: current role in clinical practice and future perspectives

Abstract

The treatment scenario of colorectal cancer (CRC) has been evolving in recent years with the introduction of novel targeted agents and new therapeutic strategies for the metastatic disease. An extensive effort has been directed to the identification of predictive biomarkers to aid patients selection and guide therapeutic choices. Pharmacogenomics represents an irreplaceable tool to individualize patients treatment based on germline and tumor acquired somatic genetic variations able to predict drugs response and risk of toxicities. The growing knowledge of CRC molecular characteristics and complex genomic makeup has played a crucial role in identifying predictive pharmacogenomic biomarkers, while supporting the rationale for the development of new drugs and treatment combinations. Clinical validation of promising biomarkers, however, is often an issue. More recently, a deeper understanding of resistance mechanisms and tumor escape dynamics under treatment pressure and the availability of novel technologies are opening new perspectives in this field. This review aims to present an overview of current pharmacogenomic biomarkers and future perspectives of pharmacogenomics in CRC, in an evolving scenario moving from a single drug-gene interactions approach to a more comprehensive genome-wide approach, comprising genomics and epigenetics.

Keywords

Colorectal cancer / pharmacogenomics / RAS / BRAF / microsatellite instability / dihydropyrimidine dehydrogenase / UDP-Glucuronosyltrasferase A1 / epidermal growth factor receptor / vascular endothelial growth factor / DNA methylation

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