Genetic and epigenetic alterations in DNA repair genes and treatment outcome of chemoradiotherapy in cervical cancer.

Atar Singh Kushwah, Shireen Masood, Rajnikant Mishra, Monisha Banerjee

Journal: Critical reviews in oncology/hematology 2024;194():104240

PMID: 38122918

Full Text on Elsevier Science View on PubMed

Abstract

Cervical cancer (CaCx) is the deadliest malignancy among women which is caused by human papillomavirus (HPV) and anthro-demographical/clinicopathological factors. HPV oncoproteins E6 and E7 target p53 and RB (retinoblastoma) protein degradation, Ataxia telangiectasia mutated (ATM), ATM-RAD3-related (ATR) inactivation and subsequent impairment of non-homologous end joining (NHEJ), homologous recombination, and base excision repair pathways. There is also an accumulation of genetic and epigenetic alterations in Tumor Growth Suppressors (TGS), oncogenes, and DNA repair genes leading to increased genome instability and CaCx development. These alterations might be responsible for differential clinical response to Cisplatin-based chemoradiotherapy (CRT) in patients. This review explores HPV-mediated DNA damage as a risk factor in CaCx development, the mechanistic role of genetic and epigenetic alterations in DNA repair genes and their association with CRT and outcome, It also explores new possibilities for the development of genetic and epigenetic-based biomarkers for diagnostic, prognostic, and molecular therapeutic interventions.

Address: Department of Urology and Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York 10029, NY, USA; Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India; Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.; Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India.; Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.; Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India. Electronic address: [email protected].

DOI: 10.1016/j.critrevonc.2023.104240

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MeSH Terms: Humans, Female, Uterine Cervical Neoplasms, Oncogene Proteins, Viral, Papillomavirus E7 Proteins, Papillomavirus Infections, DNA, DNA Repair, Epigenesis, Genetic, Treatment Outcome