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

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.

Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer

“…The DNA double stand breaks (DSBs) are the most lethal type of DNA lesions involved in many tumorigenesis initiation and progression and cause cellular genomic instability [11, 12]. These double strand breaks arise due to exposure to exogenous agents such as ionizing radiations (IRs) and alkylating agents [13].…”

Antimutagenic and antioxidant properties of the aqueous extracts of organic and conventional grapevineVitis labruscacv. Isabella leaves in V79 cells

“…There is increasing evidence that chemoprophylactic agents may prevent cancer and other diseases. In recent years, an increasing number of biomarkers of genome integrity, including telomere length and mtDNA deletions, were utilized in establishing recommended daily intakes for nutrients (Ferguson et al, 2015;Neeha and Kinth, 2013). This strategy, referred to as chemoprevention, may be pursued by means of suitable pharmacological agents and/or by dietary factors (Ferguson et al, 2005).…”

Scientific rationale for integrative and personalised strategies for pancreatic ductal adenocarcinoma management

“…Recent work implicates isothiocyanates, a key group of active ingredients in cruciferous vegetables, as a possible treatment mechanism to supplement PARP treatment [295]. In vitro studies by Banerjee et al [296] demonstrated that that pre-treatment of cells with soy-derived genistein followed by cisplatin resulted in significant loss of cell viability and potentiated apoptosis irrespective of the metastatic ability of cells.…”