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Page 26 Kaehler et al. Cancer Drug Resist 2019;2:18-30 I http://dx.doi.org/10.20517/cdr.2019.05

such as thiopurines, 5-FU or irinotecan. Pharmacogenetic testing for hereditary variants in metabolic
enzymes like TPMT and NUDT15, UGT1A1 or DPYD might be helpful to prevent patients from severe
adverse drug effects by subsequent adjustment of the drug dose or therapy alternatives. Although genetic
testing for these traits is not mandatory, implementation into the respective drug label has been performed
and genetic testing is recommended. Overall, testing for hereditary variants in these genes might be helpful
to predict adverse drug effects and improve patients’ compliance.

In contrast to variants in biotransforming enzymes, association of SNPs in drug transporters to the clinical
outcome is controversially discussed. Evidence on the predictive value of many SNPs on the respective gene
expression, function and association to drug efficacy is widely lacking. Therefore, the impact on hereditary
variants in ABC transporters on overall therapy response remains questionable.

Overall, pharmacogenetic testing of single traits might not be sufficient to explain neither interindividual
differences, nor intratumoral differences in many cases, as these underlie clonal evolution. Within the last
decades, there is much more understanding of tumor heterogeneity and complexity and research has been
widely evolved. Technologies such as whole genome analyses, RNA-seq or epigenetic analyses have been
shown to be crucial to gain deeper insights into the complexity of tumor traits and to design novel therapy
strategies and co-treatments. Especially for targeted therapy regimen, testing for presence of drugable targets
in or on tumor cells is mandatory (e.g., BCR/ABL1 or HER2). Moreover accompanied diagnostics of tumor
mutations is required for an increasing number of anticancer drugs including biologicals. Furthermore, the
invention of checkpoint blockade inhibitors like ipilimumab, nivolumab and pembrolizumab leading to re-
activation of T cell anti-tumor response revolutionized treatment in a variety of malignancies [108-110] . For
these compounds, tumor dependency on the respective target is necessary for therapeutic benefit.

Nevertheless, co-integration of genetic testing into the clinical routine for somatic and germline variants in
cancer simultaneously could be helpful to optimize therapy regimen and improve patients’ compliance and
survival.

DeClaRaTIONs
Authors’ contributions
Made substantial contributions to conception and design of this review, performed data analysis and
interpretation and wrote the manuscript: Kaehler M, Cascorbi I

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.