Germline pharmacogenomics in cancer treatment

Pharmacogenetics is the study of the genetic determinants of drug response variability, and increasing enthusiasm for implementing clinical pharmacogenetic testing is evidenced by the growing number of personalized medicine programs and the recent availability of clinical practice guidelines to facilitate the interpretation of pharmacogenetic test results. Although not all cancer therapies have germline genetic variants associated with response variability, some treatments have been found to be significantly influenced by germline variants in genes that encode enzymes involved in drug absorption, distribution, metabolism, and/or excretion. Despite challenges to demonstrate clinical utility, clinical tests are currently available for selected genes where clinical validity has largely been established. This chapter describes pharmacogenetic applications for personalized cancer treatment, including DPYD, UGT1A1, G6PD, CYP2D6, and TPMT/NUDT15.