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

: Ovarian cancer is a leading cause of death in women, particularly due to the lack of early detection methods and the aggressive nature of the disease. 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. Another subtype of ovarian cancer, known as Low-Grade Serous Ovarian Cancer (LGSOC), typically occurs in patients aged ۴۰ to ۵۵ and is linked to mutations in the KRAS and BRAF genes. Small cell carcinoma of the ovary, specifically the hypercalcemic type (SCCOHT), is a rare and aggressive ovarian cancer that mainly impacts younger women, with an average diagnosis age of about ۲۳ years. As a result, genetic testing is important for risk assessment early diagnosis, and treatment. Moreover, 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, prognosis, and pharmacodynamic monitoring. This review explores the genetic alterations, and epigenetic traits associated with ovarian cancer, while providing an overview of therapeutic strategies targeting genetic and epigenetic modulators. Methods: Data for this review were collected from peer-reviewed scientific literature using databases like PubMed, Google Scholar, and Scopus. The review included studies published between ۲۰۰۰ and ۲۰۲۳, focusing on the etiology, genetic and epigenetic mechanisms of ovarian cancer, and therapeutic advancements. Keywords included "ovarian cancer," "genetic mutations," "epigenetics," "methylation," "HDAC inhibitors," "SIRTs" 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. This genomic instability accelerates cancer progression. 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, further exacerbate tumor growth by silencing critical tumor suppressor genes like BRCA۱. Therapeutically, PARP inhibitors have shown promise in treating BRCA-mutated and HR-deficient cancers. Additionally, histone deacetylase (HDAC) and bromodomain and extra-terminal (BET) inhibitors are emerging as effective agents in restoring gene expression and enhancing chemotherapy response. Conclusion: Ovarian cancer is driven by a combination of genetic and epigenetic alterations, making it a complex disease to treat. However, advancements in understanding these mechanisms have led to more targeted therapeutic strategies. PARP inhibitors have proven effective for BRCA-mutated ovarian cancers, and emerging epigenetic therapies, such as HDAC and BET inhibitors, offer new hope for patients with chemo-resistant forms of the disease. Continued research into genetic and epigenetic interactions will be crucial for developing more personalized treatment approaches.

کلیدواژه ها:

epigenetic ، ovarian cancer ، target therapy ، genetics alterationme