Wise Management of Ovarian Cancer: On the Cutting Edge

Abstract

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations.

Development and Validation of a Prognostic Prediction Model for Postoperative Ovarian Sex Cord-Stromal Tumor Patients

“…In addition, the efficacy of chemotherapy for FIGO stage IC and advanced patients is controversial. Long-term chemotherapy can cause irreversible and severe toxicity resulting from the cumulative dose effect [ 18 ]. Hence, the present study was designed to build a more comprehensive prognostic model and to consider the effect of chemotherapy in different stages.…”

“…This finding suggests that surgery is sufficient for indolent early-stage cancer, and that chemotherapy can impair quality of life by serious adverse effects. Several single-nucleotide polymorphisms could be used to identify patients who are more likely to experience cisplatin-related toxicities [ 18 ]. Interestingly, even stage IA patients can experience relapse after administration of chemotherapy [ 36 ].…”

<p>Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets</p>

“…Opportunities for further exploration of CHK inhibitors in HGSOC arise from the observation that CHK1 inhibition is synergistic with inhibition of mitotic kinase AURKA. 42 The CHK1 inhibitor LY2603618 and the AURKA inhibitor alisertib exhibited synergistic effects in vitro in ovarian cancer cell lines, producing cell cycle arrest and inducing apoptosis. 43 WEE1 kinase and related kinase PKMYT1 phosphorylate kinase CDK1 preventing the formation of the complex with cyclin B and preventing CDK1 activation which pushes the cell through the G2 phase into mitosis.…”

P53 and PIK3CA Mutations in KRAS/HER2 Negative Ovarian Intestinal-Type Mucinous Carcinoma Associated with Mature Teratoma

“…Therefore, personalised molecular therapeutic strategies (antiestrogens, HER2 targeted therapies, RAS/RAF inhibitors, KRAS inhibitors, P53 reactivators, PI3-kinase inhibitors, …) will become crucial in the future as an alternative/complement to conventional chemotherapy [2,10]. These last years, in ovarian carcinomas associated with BRCA1/2 mutations, poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) (olaparib, niraparib, veliparib, …) demonstrated evident improvements in progressionfree survival [16][17][18]. Nevertheless, BRCA 1 or 2 mutations or homologous recombinant deficiency are not associated with mucinous carcinomas [2].…”