Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology

Abstract

Pharmacogenomics (PGx), the study of inherited genomic variation and drug response or safety, is a vital tool in precision medicine. In oncology, testing to identify PGx variants offers patients the opportunity for customized treatments that can minimize adverse effects and maximize the therapeutic benefits of drugs used for cancer treatment and supportive care. Because individuals of shared ancestry share specific genetic variants, PGx factors may contribute to outcome disparities across racial and ethnic categories when genetic ancestry is not taken into account or mischaracterized in PGx research, discovery, and application. Here, we examine how the current scientific understanding of the role of PGx in differential oncology safety and outcomes may be biased toward a greater understanding and more complete clinical implementation of PGx for individuals of European descent compared with other genetic ancestry groups. We discuss the implications of this bias for PGx discovery, access to care, drug labeling, and patient and provider understanding and use of PGx approaches. Testing for somatic genetic variants is now the standard of care in treatment of many solid tumors, but the integration of PGx into oncology care is still lacking despite demonstrated actionable findings from PGx testing, reduction in avoidable toxicity and death, and return on investment from testing. As the field of oncology is poised to expand and integrate germline genetic variant testing, it is vital that PGx discovery and application are equitable for all populations. Recommendations are introduced to address barriers to facilitate effective and equitable PGx application in cancer care.

FIG 1.

TMPT and NUDT15 allele frequencies and discovery in various populations with shared genetic ancestry. Allele frequencies: CPIC Guidelines; all alleles shown are designated no function, meaning they are unable to produce normally functioning proteins needed for drug metabolism. Most prominent variant for each allele is shown in red. CPIC, Clinical Pharmacogenetics Implementation Consortium; TMPT, gene encoding thiopurine S-methyltransferase; NUDT15, gene encoding nucleoside diphosphate-linked moiety X-type motif 15.