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 article

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.

Original languageEnglish (US)
Pages (from-to)S5-S24
JournalSeminars in Cancer Biology
Volume35
DOIs
StatePublished - Dec 1 2015

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Keywords

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

ASJC Scopus subject areas

  • Cancer Research

Cite this

Ferguson, L. R., Chen, H., Collins, A. R., Connell, M., Damia, G., Dasgupta, S., Malhotra, M., Meeker, A. K., Amedei, A., Amin, A., Ashraf, S. S., Aquilano, K., Azmi, A. S., Bhakta, D., Bilsland, A., Boosani, C. S., Chen, S., Ciriolo, M. R., Fujii, H., ... Maxwell, C. A. (2015). Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Seminars in Cancer Biology, 35, S5-S24. https://doi.org/10.1016/j.semcancer.2015.03.005