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Page 226 Mini et al. Cancer Drug Resist 2020;3:225-31 I http://dx.doi.org/10.20517/cdr.2020.10

but is also commonly associated with the use of targeted cancer therapeutics, with significant adverse event
[5]
profiles from both on and off target effects .

Moreover, intrinsic or acquired drug resistance remains a major biological and clinical phenomenon
[6]
leading to anticancer treatment failure .

Testing of cancer patients for genetic markers of efficacy or toxicity of anticancer therapeutics is
increasingly being used as a result of clinical studies based on genotype stratification, availability of
approved clinical tests and companion diagnostic biomarkers, and the continually more robust clinical
[7-9]
pharmacogenetic and pharmacogenomic information and guidelines .
This special issue of Cancer Drug Resistance is designed to provide an overview on the role of
pharmacogenetics and pharmacogenomics in the guidance of cancer treatment prescription; on the current
strategies of pharmacogenetic and pharmacogenomic discovery and their implementation in clinical
cancer drug development; and on the available information on drug labels, web resources, and guidelines,
with particular regard to the knowledge of germline variations for specific cancer drug classes and their
relevance to increased risks of adverse effects or decreased therapeutic efficacy [e.g., fluoropyrimidines,
camptothecins, thiopurines, asparaginase, immune checkpoint inhibitors and other monoclonal
antibodies, and poly-adenosyl-ribose polymerase (PARP) inhibitors]. Finally, the integration of somatic
pharmacogenomic markers into clinical practice with examples of some relevant cancer types such as
breast cancer, gastrointestinal stromal tumor (GIST), and cholangiocarcinoma, as well as an overview on
their role in the development of cancer drug resistance, is also addressed.

[10]
The article by Kaehler and Cascorbi focuses on a relevant distinction in cancer pharmacogenetics.
Cancer pharmacogenetics and pharmacogenomics imply in fact a complex conundrum of germline variants
from normal cells and somatic mutations from tumor cells. As aforesaid, somatic mutations represent
important druggable targets or biomarkers, but germline variants potentially predict adverse drug effects
or drug response. The authors evaluated the relevance of hereditary variants in absorption, distribution,
metabolism, excretion (ADME) of enzymes/proteins [such as thiopurine S-methyltransferase (TPMT),
UDP-glucuronosyltransferase (UGT1A1), and dihydropyrimidine dehydrogenase (DPD)] in predicting
genetic adverse events as well as drug transporters (ABCB1, ABCG2, and ABCC subfamilies of ATP
binding cassette transporters) and target enzymes in predicting drug efficacy with respect to both cytotoxic
agents and targeted agents.

They critically discussed gene expression regulation with regards to epigenetics and post-transcriptional
modification. They also addressed the concept that regulation of genes involved in the metabolism and
site of action of anticancer agents may be modulated by epigenetics (e.g., DNA methylation or histone
modification) at the post-transcriptional level.

[11]
Olivera et al. provided an overview of germline pharmacogenetics currently applied to the clinical
practice in oncology. On this basis, the authors described the state-of-the-art for several drugs in relation
to specific polymorphisms, as reported in pivotal tools useful for therapeutic decisions. In particular,
they mainly referred to information reported on the PharmGKB website with particular focus on the
drug/polymorphism relationships based on the levels of evidence reported in the PharmGKB Clinical
Annotations, genetic information reported on drug labels of main drug regulatory agencies, and guidelines
elaborated by international expert consortia (e.g., Clinical Pharmacogenetics Implementation Consortium
and Dutch Pharmacogenetics Working Group). On this basis, recommendations for the administration
of thiopurines in relation to genetic polymorphisms of TPMT, fluoropyrimidines in relation to those of