Genetic and Epigenetic Insights in Ovarian Cancer: Unveiling Biomarkers and Therapeutic Advances

Introduction. Ovarian cancer is a leading cause of death in women, particularly due to the lack of early detection and aggressive nature of the disease (۱). The majority of ovarian cancers are epithelial ovarian cancers (EOC), affecting post-menopausal women, with lifestyle and genetic predispositions like BRCA mutations contributing to risk (۲). Another subtype of ovarian cancer, known as low-grade serous ovarian cancer (LGSOC), is typically linked to mutations in the KRAS and BRAF genes. Furthermore, small cell carcinoma of the ovary, specifically the hypercalcemic type (SCCOHT), is a rare and aggressive type that mainly impacts younger women, with an average diagnosis age of about ۲۳ years (۳). Epigenetic abnormalities, such as histone modifications, DNA methylation, and micro-RNA dysregulation, are now recognized as key factors in the development and progression of ovarian cancer, with their accumulation being linked to more advanced stages and grades of the disease. Epigenetic abnormalities are relatively stable, linked to specific disease subtypes, and detectable in circulating serum, making them promising biomarkers for diagnosis and prognosis (۴). This review explores the genetic and epigenetic traits associated with ovarian cancer while providing an overview of therapeutic strategies targeting genetic and epigenetic modulators. Methods. Data were collected from peer-reviewed scientific literature using databases like PubMed, Google Scholar, and Scopus. The review included studies published between ۲۰۰۳ and ۲۰۲۴, focusing on the etiology, genetic and epigenetic mechanisms of ovarian cancer, as well as therapeutic advancements. Keywords included "ovarian cancer," "genetic mutations," "epigenetics alterations," "HDAC inhibitors," and "epigenetic therapy." Results. Ovarian cancer is strongly linked to genetic mutations, particularly in the BRCA۱ and BRCA۲ genes, which are responsible for defects in homologous recombination (HR) repair mechanisms, able to accelerate cancer progression (۵). Mutations in mismatch repair (MMR) genes, such as MSH۲ and MLH۱, also increase the risk of Lynch syndrome-associated ovarian cancer. Epigenetic changes such as promoter hypermethylation and histone modifications could exacerbate tumor growth by silencing critical tumor suppressor genes like BRCA۱ (۶). Therapeutically, PARP inhibitors have shown promise in treating BRCA-mutated and HR-deficient cancers (۷). Additionally, histone deacetylase (HDAC) and bromodomain and extra-terminal (BET) inhibitors are emerging as effective factors in restoring gene expression and enhancing chemotherapy response (۸). It is extremely promising that epigenetic regulators have exhibited anti-tumor effects for ovarian cancer in clinical trials. EZH۲ inhibition is one of the most promising therapies for CARM۱-overexpressing HGSOC, ARID۱A-mutant OCCC/OEC, and SMARCA۲/۴-deficient SCCOHT (۹). Conclusion: Novel research in the field of genetics and epigenetics opened new insight into pathogenesis of OC and provided further opportunities for identifying biomarkers to diagnose and target therapeutic strategies. Furthermore, cancer genes that are epigenetically silenced or activated present new opportunities for therapeutic intervention using demethylating agents and HDAC inhibitors, either alone or in combination therapies. Epigenetic treatment strategies are advancing into new areas, offering innovative and promising approaches with the potential to improve patient survival. However, significant challenges remain in understanding the underlying science and in translating ovarian cancer epigenetics into effective clinical applications (۱۰).

کلیدواژه ها:

Epigenetics ، Ovarian Cancer ، Target therapy ، Genetics alteration