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

Ludivine Dion,Sylvie Jaillard,Thibault De La Motte Rouge,Fabrice Foucher,Krystel Nyangoh Timoh,Isis Carton,Vincent Lavoué,Sébastien Henno,Hugo Sardain,Jean Levêque,Susie Brousse

doi:10.3390/jcm9072239

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.

Highlights

Epithelial ovarian cancer (EOC) affects one in every 60 women in industrialized countries [1] and has an annual incidence of approximately 43,000 cases worldwide [2]
Surgery combined with carboplatin and paclitaxel chemotherapy was the current standard of care prior to the recent development of antiangiogenic agent bevacizumab, which resulted in a modest improvement in progression-free survival in women with ovarian cancer with a poor prognosis, i.e., women with stages other than FIGO stage IIIc with residual disease after surgery and FIGO stage IV [3]
Between 10% and 15% of women with EOC are genetically predisposed to ovarian cancer, and 90% have a BReast CAncer (BRCA) mutation (BRCA1 or BRCA2)

Summary

Introduction

Epithelial ovarian cancer (EOC) affects one in every 60 women in industrialized countries [1] and has an annual incidence of approximately 43,000 cases worldwide [2]. Surgery combined with carboplatin and paclitaxel chemotherapy was the current standard of care prior to the recent development of antiangiogenic agent bevacizumab, which resulted in a modest improvement in progression-free survival (four months) in women with ovarian cancer with a poor prognosis, i.e., women with stages other than FIGO stage IIIc with residual disease after surgery and FIGO stage IV [3]. We provide an updated overview of the different molecular profiles described for EOC in the literature and discuss their role in the current and future management of this disease

Methods

Results

Conclusion