Germline variants in cancer therapy

Meike Kaehler; Ingolf Cascorbi

doi:10.20517/cdr.2019.05

Germline variants in cancer therapy

Cancer Drug Resist. 2019 Mar 19;2(1):18-30. doi: 10.20517/cdr.2019.05. eCollection 2019.

Authors

Meike Kaehler¹, Ingolf Cascorbi¹

Affiliation

¹ Institute for Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel D-24105, Germany.

Abstract

Cancer pharmacogenetics implies a complex combination of germline variants from the patient and somatic mutations in tumor cells. Somatic mutations meanwhile have become drugable targets or biomarkers, whereas germline mutations potentially predict adverse drug effects or drug response. Here, we evaluate hereditary variants in biotransforming enzymes and drug transporters, such as thiopurine S-methyltransferase, UDP-glucuronosyltransferase (UGT1A1), dihydropyrimidine dehydrogenase (DPD), as well as ABC transporters (ABCB1, ABCG2 and ABCC subfamily) with respect to cytostatics and targeted therapies. Furthermore, gene expression regulation with regards to epigenetics and posttranscriptional modification are discussed.

Keywords: Pharmacogenetics; anticancer drugs; cytotoxic drugs; drug metabolism; drug resistance; drug transporter; toxicity.

Publication types

Review