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Article Dans Une Revue Journal of Clinical Medicine Année : 2020

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

Résumé

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 toBRCA1orBRCA2mutations. 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 aBRCAmutation. Tumors withBRCAmutations 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 inBRCA-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.
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Dates et versions

hal-02928442 , version 1 (29-09-2020)

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Ludivine Dion, Isis Carton, Sylvie Jaillard, Krystel Nyangoh Timoh, Sébastien Henno, et al.. The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer. Journal of Clinical Medicine, 2020, 9 (7), ⟨10.3390/jcm9072239⟩. ⟨hal-02928442⟩
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