Advances and challenges in hereditary cancer pharmacogenetics

Expert Opin Drug Metab Toxicol. 2017 Jan;13(1):73-82. doi: 10.1080/17425255.2017.1233965. Epub 2016 Sep 16.

Abstract

Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Moreover, the association between genetic variants of drug transporters with the clinical outcome is comprehensively discussed. Expert opinion: Precision therapy in the field of oncology is developing tremendously. There are a number of somatic tumor genetic markers that are indicative for treatment with anti-cancer drugs. By contrast, for some hereditary variants, recommendations have been developed. Although we have vast knowledge on the association between drug transporter variants and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. Further developments in research may lead to the discovery of rare, but functionally relevant single nucleotide polymorphisms and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.

Keywords: ABC transporters; Precision medicine; adverse events; drug labeling; multi drug resistance.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Biomarkers, Tumor / genetics
  • Genetic Variation
  • Humans
  • Membrane Transport Proteins / genetics
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Pharmacogenetics / methods*
  • Polymorphism, Single Nucleotide
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Membrane Transport Proteins