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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11th International Conference on
Journal of Medical Oncology and Therapeutics | Volume 3
Vitale Ilio et al., J Med Oncl Ther 2018, Volume 3
REPLICATION STRESS RESPONSE IN
CSCs: MOLECULAR MECHANISMS
AND THERAPEUTIC IMPLICATION
Vitale Ilio1, Manic G2, Sistigu A2,3 and De Maria R3
1University of Rome “Tor Vergata”, Rome, Italy
2Elena National Cancer Institute, Rome, Italy
3Catholic University “Sacro Cuore”, Italy
Cancer stem cells (CSCs) are subpopulations of multipotent SCs
responsible for the initiation, long-term clonal maintenance, growth
and spreading of most human neoplasms, including colorectal cancer
(CRC). CSCs reportedly share with embryonic and adult SCs a very robust
DNA damage response (DDR), which favors their survival and drives the
resistance to endogenous and exogenous genotoxins. Taking advantage
of a panel of CRC patient-derived tumorspheres enriched for CSCs (CRC-
SCs), we demonstrated that CSCs have high, although heterogeneous,
levels of replication stress (RS). By performing genetic and cytogenetic
analyses, we provided evidence that RS in CRC-SCs is boosted
endogenously by p53 deficiency and the presence of supernumerary
chromosomes. We also elucidated the tight, but plastic and multipronged
RS response put in place by CSCs to set the threshold of and ensure
tolerability to RS, which involves CHK1, PARP and some components of
the homologous recombination repair. Of relevance for cancer therapy, we
showed that such a robust and efficient response confers to replication-
stressed CSCs elevated dependency on specific component(s) such
as CHK1. Nonetheless, the redundancy and rewiring potential of RS
response also favors the acquisition of resistance to RS-modulating and
DNA-damaging regimens. Driven by this paradoxical evidence and based
on the levels of RS at baseline, we designed dedicated RS response-
targeting strategies with long-term CSC depleting effectiveness.
Vitale Ilio has received his PhD in 2006 for Mo-
lecular Characterization of Mitotic Catastrophe.
During his six-year Post-doctoral studies in
France, he investigated the role of aneuploidy/
tetraploidy in tumorigenesis uncovering sur-
veillance mechanisms surveying cell ploidy
(EMBOJ 2010, Science 2012). He currently is a
Group Leader and Adjunct Professor in Neuro-
biology at the University of Rome “Tor Vergata”
working on the link between CSCs, chromosom-
al instability, and tumor immunity. His group
recently identified a novel strategy for the de-
pletion of CSCs based on CHK1 inhibition (Gut
2017, Mol Cell 2017). He is the Executive Editor
of Molecular and Cellular Oncology, Subject Edi-
tor in the Reference Module in Life Sciences and
served as Editor for several books. He received
the Young Scientist Award from the European
Environmental Mutagenesis Society (2013). He
is Author of >100 ISI papers (including Science,
Nat Med, Nat Rev Mol Cell Biol., Nat Cell Biol).
“h” index: 34.
BIOGRAPHY