The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer.

Abstract

Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20-30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.

• Authors: Ludivine Dion, Isis Carton, Sylvie Jaillard, Krystel Nyangoh Timoh, Sébastien Henno, Hugo Sardain, Fabrice Foucher, Jean Levêque, Thibault de la Motte Rouge, Susie Brousse, Vincent Lavoué
• Journal: Journal of clinical medicine (J Clin Med) Vol. 9 Issue 7 (Jul 15 2020) ISSN: 2077-0383 [Print] Switzerland
• PMID: 32679669 (Publication Type: Journal Article, Review)