The Impact of Pharmacogenetics on Colorectal Cancer Therapy: A Move toward Rational Therapeutic Decisionmaking in Clinical Practice

Abstract

Despite recent progress in the investigation and therapy of colorectal cancer (CRC), the disease still remains one of the major causes of cancer-related deaths worldwide. In the past decade, with the introduction of new cytotoxic and targeting agents, significant improvements have been made in response rates, progression-free survival, and overall survival of metastatic colorectal cancer (mCRC) patients. In spite of these improvements, a significant number of CRC patients undergo chemotherapy for advanced disease without any significant benefit, and may suffer from severe adverse effects. In this post-genomic era, the individualization of cancer chemotherapy through the study of pharmacogenetics is becoming an everattainable goal. Pharmacogenetic studies and pharmacogenomics (a polygenic approach to pharmacogenetic studies) have shown that polymorphisms in genes related to drug metabolism, transport, and drug targets contribute to interindividual differences in drug efficacy and toxicities. Validation of predictive and prognostic molecular markers will enable clinicians in the tailoring of chemotherapy for each patient based on the molecular profile of both the patient and tumor. Currently I am focusing on the results of studies assessing the effects of gene polymorphisms in drug metabolizing enzymes and drug targets on the response and toxicity to commonly used clinical anticancer drugs for CRC patients, with the purpose of selecting the optimal drug therapy and dosage for each patient.