The use of genomic information to optimize cancer chemotherapy

Abstract

The field of pharmacogenomics is focused on the characterization of genetic factors contributing to the response of patients to pharmacological interventions. Drug response and toxicity are complex traits; therefore the effects are likely influenced by multiple genes. The investigation of the genetic basis of drug response has evolved from a focus on single genes to relevant pathways to the entire genome. Preclinical (cell-based models) and clinical genome-wide association studies (GWAS) in oncology provide an unprecedented opportunity for a comprehensive and unbiased assessment of the heritable factors associated with drug response. The primary challenge with attempting to identify pharmacogenomic markers from clinical studies is that they require a homogeneous population of patients treated with the same dosage regimen and minimal confounding variables. Therefore, the development of cell-based models for pharmacogenomic marker identification has utility for the field since performing these types of studies in humans is difficult and costly. This review intends to provide a current report on the status of genomic studies in oncology, the methods for discovery, and implications for patient care. We present a perspective and summary of the challenges and opportunities in translating heritable genomic discoveries to patients.