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

Lynnette R. Ferguson, Helen Chen, Andrew R. Collins, Marisa Connell, Giovanna Damia, Santanu Dasgupta, Meenakshi Malhotra, Alan K. Meeker, Amedeo Amedei, Amr Amin, S. Salman Ashraf, Katia Aquilano, Asfar S. Azmi, Dipita Bhakta, Alan Bilsland, Chandra S. Boosani, Sophie Chen, Maria Rosa Ciriolo, Hiromasa Fujii, Gunjan GuhaDorota Halicka, William G. Helferich, W. Nicol Keith, Sulma I. Mohammed, Elena Niccolai, Xujuan Yang, Kanya Honoki, Virginia R. Parslow, Satya Prakash, Sarallah Rezazadeh, Rodney E. Shackelford, David Sidransky, Phuoc T. Tran, Eddy S. Yang, Christopher A. Maxwell

Research output: Contribution to journalReview articlepeer-review

189 Scopus citations


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.

Original languageEnglish
Pages (from-to)S5-S24
JournalSeminars in Cancer Biology
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
The following funding agencies supported the research: Italian Ministry of University and Research and the University of Florence (A. Amedia); Terry Fox Foundation, UAEU Program for Advanced Research, Al-Jalila Foundation and Zayed Center for Health Sciences (A. Amin); Italia Ministry of Education, University and Research- Miur , PRIN 20125S38FA_002 (K. Aquilano); University of Glasgow, Beatson Oncology Centre Fund , CRUK grant C301/A14762 (A. Bilsland and W.N. Keith); Child and Family Research Institute PhD studentship (H. Chen); Michael Cuccione childhood cancer research foundation fellowship (M. Connell); Ovarian Prostate Cancer Research Trust Laboratory (S. Chen); University of Oslo (A.R. Collins); Italian Association for Cancer Research AIRC IG 10636 (M.R. Ciriolo); Elsa U Pardee Foundation (S. Dasgupta); Auckland Cancer Society Research Centre, University of Auckland (L. Ferguson and V. Parslow); National Institutes of Health (H.D. Halicka); Ministry of Education, Culture, Sports, Science and Technology, Japan , No. 24590493 (K. Honoki); CIHR, in partnership with the Avon Foundation for Women , OBC 134038 (C.A. Maxwell); NIH/NCI RO1CA172380 , DOD W81WH1210545 , DOD W81XWH12PCRPTIA , NIH/NCI P30CA006973 , NIH/NCI RCI RFA0D09009 , NIH/NCI 5R01 CA132996-03 (A. Meeker); Italian Ministry of University and University of Italy (E. Niccolai); CIHR MOP 64308 (S. Prakash); Department of Biology, University of Rochester (S. Rezazadeh); Patrick C. Walsh Prostate Cancer Research Fund, the Department of Defense ( W81XWH-11-1-0272 and W81XWH-13-1-0182 ), Commonwealth Foundation, Uniting Against Lung Cancer, a Sidney Kimmel Translational Scholar award ( SKF-13-021 ), an ACS Scholar award ( 122688-RSG-12-196-01-TBG ) and the NIH ( 1R01CA166348 ) (P.T. Tran); Susan G. Komen Foundation, AACR, Gabrielle's Angel Foundation, Eli Lilly, and Bristol Myers Squibb (E.S. Yang).

Publisher Copyright:
© 2015 The Authors.


  • Cancer prevention
  • Cancer therapy
  • DNA damage
  • Genomic instability
  • Nutraceutical

ASJC Scopus subject areas

  • Cancer Research


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