TY - JOUR
T1 - Genomic instability in human cancer
T2 - Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition
AU - Ferguson, Lynnette R.
AU - Chen, Helen
AU - Collins, Andrew R.
AU - Connell, Marisa
AU - Damia, Giovanna
AU - Dasgupta, Santanu
AU - Malhotra, Meenakshi
AU - Meeker, Alan K.
AU - Amedei, Amedeo
AU - Amin, Amr
AU - Ashraf, S. Salman
AU - Aquilano, Katia
AU - Azmi, Asfar S.
AU - Bhakta, Dipita
AU - Bilsland, Alan
AU - Boosani, Chandra S.
AU - Chen, Sophie
AU - Ciriolo, Maria Rosa
AU - Fujii, Hiromasa
AU - Guha, Gunjan
AU - Halicka, Dorota
AU - Helferich, William G.
AU - Keith, W. Nicol
AU - Mohammed, Sulma I.
AU - Niccolai, Elena
AU - Yang, Xujuan
AU - Honoki, Kanya
AU - Parslow, Virginia R.
AU - Prakash, Satya
AU - Rezazadeh, Sarallah
AU - Shackelford, Rodney E.
AU - Sidransky, David
AU - Tran, Phuoc T.
AU - Yang, Eddy S.
AU - Maxwell, Christopher A.
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Cancer prevention
KW - Cancer therapy
KW - DNA damage
KW - Genomic instability
KW - Nutraceutical
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U2 - 10.1016/j.semcancer.2015.03.005
DO - 10.1016/j.semcancer.2015.03.005
M3 - Review article
C2 - 25869442
AN - SCOPUS:84926686973
SN - 1044-579X
VL - 35
SP - S5-S24
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
ER -