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Introduction
The human body is continuously exposed to mutagens that cause DNA damage, which is swiftly countered by sophisticated DNA repair mechanisms essential for preserving genomic stability. This dynamic balance between DNA damage and repair has critical implications for aging and diseases like cancer. Numerous cancers, including those of the colon, lung, breast, bladder, and oesophagus, have been linked to mutations in DNA repair proteins such as DNA polymerase β (Pol β)¹. Recent research has increasingly focused on Pol β mutations in ovarian cancer, a major global health concern, particularly in India, where it ranks third in cancer frequency and eighth in overall cancer prevalence²˒³. Ovarian cancer is a significant contributor to cancer-related mortality worldwide, largely due to late-stage diagnosis, which severely limits treatment options. In India, ovarian cancer accounts for 3.44% of all cancer cases and 3.34% of cancer-related deaths⁴˒⁶. While early detection at Stage I yields a promising five-year survival rate of 94%, the majority of cases are diagnosed at Stages III and IV, where the survival rate drops to 28%⁶. Globally, this underscores the need for improved diagnostic methods and more effective treatments. Studies suggest that defects in DNA repair mechanisms can increase tumor sensitivity to chemotherapy, as evidenced by the efficacy of PARP inhibitors in BRCA1-deficient cancers⁸˒⁹. In addition to PARP inhibitors, other DNA repair enzymes, such as glycosylases, phosphodiesterases, and Pol β, are being actively investigated as therapeutic targets. Inhibitors of these enzymes, particularly when combined with DNA-damaging agents like radiation or alkylating agents, have demonstrated potential in selectively inducing cancer cell death by exploiting cancer-specific DNA repair deficiencies⁹˒¹⁰. This therapeutic approach offers a promising strategy to improve the efficacy of conventional treatments for ovarian cancer.
Ovarian cancer remains a formidable health issue worldwide, including in India, where advanced-stage diagnosis presents significant treatment challenges. Enhanced understanding of the molecular mechanisms underlying DNA repair deficiencies in ovarian cancer, combined with the development of targeted therapies, holds potential for improving outcomes for affected women. Epithelial ovarian cancer is a heterogeneous disease with five major subtypes: high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous, with high-grade serous being the most prevalent. The extensive genetic instability and lack of prominent driver mutations complicate molecular profiling in many forms of the disease⁷˒¹¹. While homologous...