New approaches in ovarian cancer based on genetics and carcinogenesis hypotheses (Review).

Ovarian cancer is the leading cause of death among gynecological malignancies and its incidence is rising in the last decades especially in developed countries. High-grade serous ovarian cancer (HGSOC) represents 70% of ovarian cancers. Oral contraceptive use and salpingo-oophorectomy or salpingectomy are well known protective factors against development of ovarian cancer. Identification of specific mutations associated with a high risk of developing ovarian cancer, especially BRCA1/2 mutation and TP53 mutations, has paved the way for implementation of new strategies for early diagnosis and therapy. Hereditary forms of ovarian cancer account for 5-10% and have BRCA1/2 gene mutations or TP53 mutations. BRCA1/2 gene mutations appear in 22% of HGSOC and are associated with the defective homologous repair (HR)/DNA repair pathway. Genetic testing in ovarian cancer is important for risk assessment and therapeutic options. Although 'universal genetic testing' is not recommended yet, the procedure remains highly recommended in women with high risk. Genes involved in the development of ovarian cancer as TP53 may be targeted by gene therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors may enhance the cytotoxic effect of DNA-damaging chemotherapy, and induce synthetic lethality in cases with BRCA1/2 mutations. Other strategies are designed to target pathways driven by various gene mutations, including the use of tyrosine kinase inhibitors in low-grade serous ovarian cancer (LGSOC), or the use of drugs, which target growth factors, or epigenetic events including methylation, and acetylation of genes. The tubal involvement in ovarian carcinogenesis provides an important tool for the clinician to implement risk-reducing strategies including salpingo-oophorectomy or salpingectomy in high-risk cases at appropriate ages.