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Crisafulli et al. Cancer Drug Resist 2019;2:225-41 I http://dx.doi.org/10.20517/cdr.2018.008 Page 237

lethality. A synthetic lethality event occurs when two or more genes are simultaneously perturbed and
exposure to a drug results in cellular or organism death/impairment. Large-scale analysis in yeast and
human cells have already resulted in the identification of actionable networks of conserved, synthetic lethal
interactions.

An additional level of cancer pharmacogenomics will be reached by single cell omics analyses. These will
obtain information from individual cancer cells, to identify both common regulatory themes as well as
population heterogeneity. This is expected to lead to the identification of subpopulations of therapy-resistant
[94]
cells and of the corresponding control pathways .

A key role is all the analyses above will be provided by next-generation bioinformatic approaches, which will
be instrumental in taking the greatest advantage of whole-genome sequencing at population levels and of
[95]
single-cell measurements .
According to National Comprehensive Cancer Network, NGS-based pharmacogenetic/pharmacogenomic
assays still are qualified as second-tier tests. The growing body of pharmacogenomic data may soon allow
to go well beyond such a stage and to provide strong means to guide clinicians in the selection of safer and
[17]
more effective therapies .

DEClARATIONS
Acknowledgments
We thank Dr. A. Capra for web data analysis during the preparation of the manuscript and Prof. S.
Cuzzocrea and L. Chiara for their unfailing support throughout the study.

Authors’ contributions
Made substantial contributions to the conception and design of the study: Crisafulli C, Alberti S
Performed analyses of the meta-data from DNA sequence databases: Crisafulli C, Calabrò M, Epasto LM
Performed the comparative profiling of the NGS analyses: Romeo PD
Contributed to data acquisition and took part to the drafting, discussion and revision of the manuscript text:
Crisafulli C, Romeo PD, Calabrò M, Epasto LM, Alberti S

Availability of data and materials
Not applicable.

Financial support and sponsorship
The support of the Italian Ministry of Development - FESR, of the Italian Ministry of University and
Research (Smart Cities and Communities SCN_00558) and of the Policlinico “G. Martino” of Messina
is gratefully acknowledged. None of the funding bodies had any role in the manuscript design, in the
collection, analysis and interpretation of the data, and in the writing of the manuscript.

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

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.