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

Journal of Cancer Metastasis and Treatment 2018年第1期4卷 146-170页

作者： Francesca Battaglin Alberto Puccini Madiha Naseem Marta Schirripa Martin DBerger Ryuma Tokunaga Michelle McSkane Taline Khoukaz Shivani Soni Wu Zhang Heinz-Josef Lenz Division of Medical Oncology Norris Comprehensive Cancer CenterKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Medical Oncology Unit 1 Clinical and Experimental Oncology DepartmentVeneto Institute of Oncology IOV-IRCCSPadua 35128Italy Department of Medical Oncology University Hospital of BernBern 3010Switzerland

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.

关键词： 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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