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Battaglin et al. J Cancer Metastasis Treat 2018;4:12                Journal of Cancer
               DOI: 10.20517/2394-4722.2018.04                           Metastasis and Treatment




               Review                                                                        Open Access


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



               Francesca Battaglin , Alberto Puccini , Madiha Naseem , Marta Schirripa , Martin D. Berger , Ryuma
                                                               1
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                                1,2
               Tokunaga , Michelle McSkane , Taline Khoukaz , Shivani Soni , Wu Zhang , Heinz-Josef Lenz 1
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               1 Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California,
               Los Angeles, CA 90033, USA.
               2 Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV - IRCCS, Padua
               35128, Italy.
               3 Department of Medical Oncology, University Hospital of Bern, Bern 3010, Switzerland.
               Correspondence to: Prof. Heinz-Josef Lenz, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School
               of Medicine, University of Southern California, 1441 Eastlake Avenue, Suite 3456, Los Angeles, CA 90033, USA. E-mail: lenz@
               med.usc.edu
               How to cite this article: Battaglin F, Puccini A, Naseem M, Schirripa M, Berger MD, Tokunaga R, McSkane M, Khoukaz T, Soni
               S, Zhang W, Lenz HJ. Pharmacogenomics in colorectal cancer: current role in clinical practice and future perspectives. J Cancer
               Metastasis Treat 2018;4:12. http://dx.doi.org/10.20517/2394-4722.2018.04
               Received: 26 Jan 2018    First Decision: 8 Feb 2018    Revised: 10 Feb 2018    Accepted: 11 Feb 2018    Published: 7 Mar 2018
               Science Editor: Godefridus J. Peters    Copy Editor: Jun-Yao Li    Production Editor: Cai-Hong Wang



               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

                           © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
                sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
                as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
                and indicate if changes were made.


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