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Kaehler et al. Cancer Drug Resist 2019;2:18-30 Cancer
DOI: 10.20517/cdr.2019.05 Drug Resistance

Review Open Access

Germline variants in cancer therapy

Meike Kaehler, Ingolf Cascorbi

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

Correspondence to: Prof. Ingolf Cascorbi, Institute for Experimental and Clinical Pharmacology, University Hospital Schleswig-
Holstein, Arnold-Heller-Str. 3, Campus Kiel, Kiel D-24105, Germany. E-mail: cascorbi@pharmakologie.uni-kiel.de

How to cite this article: Kaehler M, Cascorbi I. Germline variants in cancer therapy. Cancer Drug Resist 2019;2:18-30.
http://dx.doi.org/10.20517/cdr.2019.05

Received: 13 Dec 2018 First Decision: 21 Dec 2018 Revised: 11 Feb 2019 Accepted: 15 Feb 2019 Published: 19 Mar 2019

Science Editor: Enrico Mini Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

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, cytotoxic drugs, anticancer drugs, toxicity, drug resistance, drug metabolism, drug
transporter

INTRODUCTION
The tumor cell genome consists of a complex combination of germline and somatic mutations that
[1]
potentially interfere with anticancer treatment . Most genetic mutations in a tumor cell are somatic and are
increasingly implicated in targeted therapy with considerable therapeutic benefit. Nevertheless, germline
variants may also contribute to interindividual differences in anti-cancer drug response leading to drug
resistance, but also to adverse drug effects. Thus, somatic mutations are often associated with treatment
[2,3]
efficacy, while hereditary variants are more often considered to address adverse drug effects . As anticancer
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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