Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.

Author: Ferguson LR1, Chen H2, Collins AR3, Connell M2, Damia G4, Dasgupta S5, Malhotra M6, Meeker AK7, Amedei A8, Amin A9, Ashraf SS10, Aquilano K11, Azmi AS12, Bhakta D13, Bilsland A14, Boosani CS15, Chen S16, Ciriolo MR11, Fujii H17, Guha G13, Halicka D18, Helferich WG19, Keith WN14, Mohammed SI20, Niccolai E8, Yang X19, Honoki K17, Parslow VR21, Prakash S6, Rezazadeh S12, Shackelford RE22, Sidransky D23, Tran PT24, Yang ES25, Maxwell CA26.
Affiliation:
1Discipline of Nutrition, University of Auckland, Auckland, New Zealand. Electronic address: l.ferguson@auckland.ac.nz. 2Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada. 3Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway. 4Department of Oncology, Instituti di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. 5Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, United States. 6School of Pharmacy, University College Cork, Cork, Ireland. 7Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States. 8Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 9Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates; Faculty of Science, Cairo University, Cairo, Egypt. 10Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates. 11Department of Biology, Università di Roma Tor Vergata, Rome, Italy. 12Department of Biology, University of Rochester, Rochester, United States. 13School of Chemical and BioTechnology, SASTRA University, Thanjavur, Tamil Nadu, India. 14Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. 15Department of BioMedical Sciences, Creighton University, Omaha, NE, United States. 16Department of Research & Development, Ovarian and Prostate Cancer Research Trust Laboratory, Guildford, Surrey, United Kingdom. 17Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Nara, Japan. 18New York Medical College, Valhalla, NY, United States. 19Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Champaign, IL, United States. 20Department of Comparative Pathobiology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, United States. 21Discipline of Nutrition, University of Auckland, Auckland, New Zealand. 22Department of Pathology, Louisiana State University Health Shreveport, Shreveport, LA, United States. 23Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. 24Departments of Radiation Oncology & Molecular Radiation Sciences, Oncology and Urology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, United States. 25Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, United States. 26Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, Canada. Electronic address: cmaxwell@cfri.ca.
Conference/Journal: Semin Cancer Biol.
Date published: 2015 Apr 10
Other: Pages: S1044-579X(15)00020-6 , Special Notes: doi: 10.1016/j.semcancer.2015.03.005. , Word Count: 228


Abstract
Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology.
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
KEYWORDS:
Cancer prevention; Cancer therapy; DNA damage; Genomic instability; Nutraceutical
PMID: 25869442

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