Personalizing cancer treatment using gene activity scores with the NIH Medical Genetics Summaries.

Abstract

e22000 Background: Oncology professionals need to access a wide range of genetic tests, including tests for cancer biomarkers, predisposition to hereditary cancers, and pharmacogenetic tests. While pharmacogenetic testing is fundamental to personalized medicine, the adoption of testing has been slow, partly due to a lack of readily accessible information about new developments, such as gene activity scores. Methods: Medical Genetics Summaries (MGS) was created to bridge the translation gap between genetic test results and personalized treatment plans. MGS is a free, regularly updated, peer-reviewed pharmacogenetics resource. The complete set of summaries can be browsed online or saved as PDF (www.ncbi.nlm.nih.gov/books/n/gtrbook). Excerpts of the summaries can be found via PubMed (www.pubmed.gov) and MedGen (www.ncbi.nlm.nih.gov/medgen). Results: Of the 45 drug-gene interactions included so far in MGS, 10 are commonly used cancer drugs. These include capecitabine (Xeloda) and fluorouracil (Adrucil), which are both fluoropyrimidines—antimetabolite drugs used in the treatment of colon cancer and breast cancer. The DPYD gene encodes the rate-limiting enzyme for the breakdown of fluoropyrimidines. Patients with specific variations in the DPYD gene (e.g., DPYD*2A, DPYD*13) have decreased or absent enzyme activity. In these patients, the standard recommended dose of fluoropyrimidine can cause life-threatening bone marrow suppression and neurotoxicity. MGS presents the dosing recommendation for each DPYD phenotype, which are clearly defined using the recently assigned DPYD activity scores, from authoritative professional guidelines such as the National Comprehensive Cancer Network (NCCN) and the Clinical Pharmacogenetics Implementation Consortium (CPIC), in addition to the FDA. MGS also provides an overview of the drug (drug class, mechanism of action, adverse events), an introduction to the gene(s) and significant alleles, and guidance on genetic testing—along with links to the relevant tests in the NIH Genetic Testing Registry (GTR, www.ncbi.nlm.nih.gov/gtr). Conclusions: This presentation will demonstrate how NIH precision medicine resources, with a focus on MGS, can simplify the process of ordering and interpreting pharmacogenetic tests and efficiently tailor care for your patient.