ABSTRACT
Introduction: 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.
Article highlights
Companied genetic diagnostics of specific somatic tumor mutations is a prerequisite of therapeutic indications of modern anticancer regimen.
Pharmacogenetic traits in ADME gene may contribute to the interindividual variability of treatment response of various anticancer drugs.
Recommendations for application of pharmacogenetics information have been developed by CPIC in order to minimize the risk of adverse events e.g. of thiopurine analogues, irinotecane or 5-fluorouracil.
Efflux transporters contribute to the phenomenon of drug resistance. Data on association of hereditary genetic variants however is inconsistent and/or have a low predictive value.
Precision therapy should consider a broad pattern of molecular biomarkers including the patients’ phenotype.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.