Page 47 - Read Online

Crisafulli et al. Cancer Drug Resist 2019;2:225-41 Cancer
DOI: 10.20517/cdr.2018.008 Drug Resistance

Review Open Access

Pharmacogenetic and pharmacogenomic discovery
strategies

Concetta Crisafulli , Petronilla Daniela Romeo , Marco Calabrò , Ludovica Martina Epasto , Saverio
2
1
1
2
Alberti 1,2
1 Department of Biomedical Sciences - BIOMORF, University of Messina, via Consolare Valeria, 98125 Messina, Italy.
2 Unit of Medical Genetics, University of Messina, via Consolare Valeria, 98125 Messina, Italy.
Correspondence to: Prof. Saverio Alberti, Unit of Medical Genetics, BIOMORF Department of Biomedical Sciences, University of
Messina, via Consolare Valeria, 98125 Messina, Italy. E-mail: salberti@unime.it
How to cite this article: Crisafulli C, Romeo PD, Calabrò M, Epasto LM, Alberti S. Pharmacogenetic and pharmacogenomic
discovery strategies. Cancer Drug Resist 2019;2:225-41. http://dx.doi.org/10.20517/cdr.2018.008

Received: 18 Dec 2018 First Decision: 18 Feb 2019 Revised: 22 Mar 2019 Accepted: 26 Mar 2019 Published: 19 Jun 2019

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

Abstract
Genetic/genomic profiling at a single-patient level is expected to provide critical information for determining inter-
individual drug toxicity and potential efficacy in cancer therapy. A better definition of cancer subtypes at a molecular
level, may correspondingly complement such pharmacogenetic and pharmacogenomic approaches, for more effective
personalized treatments. Current pharmacogenetic/pharmacogenomic strategies are largely based on the identification
of known polymorphisms, thus limiting the discovery of novel or rarer genetic variants. Recent improvements in cost
and throughput of next generation sequencing (NGS) are now making whole-genome profiling a plausible alternative for
clinical procedures. Beyond classical pharmacogenetic/pharmacogenomic traits for drug metabolism, NGS screening
programs of cancer genomes may lead to the identification of novel cancer-driving mutations. These may not only
constitute novel therapeutic targets, but also effector determinants for metabolic pathways linked to drug metabolism.
An additional advantage is that cancer NGS profiling is now leading to discovering targetable mutations, e.g., in
glioblastomas and pancreatic cancers, which were originally discovered in other tumor types, thus allowing for effective
repurposing of active drugs already on the market.

Keywords: Pharmacogenetics, pharmacogenomics, cancer, next-generation sequencing, genomic variants

INTRODUCTION
Advances in cancer treatment over the last decades have more and more relied on identifying therapy-
[1]
responsive subgroups on the basis of evolving tumor subgroup classifications , as based on pathological
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.cdrjournal.com