Ovarian cancer

Epithelial ovarian cancer (EOC) describes a group of diseases characterized by differing pathogeneses, molecular profiles, histologies and prognoses. The low incidence of each distinct histological type of EOC poses challenges for obtaining an accurate diagnosis, robust evidence to guide management, and a mechanistic understanding to ensure availability of effective therapies. Most EOCs, including high-grade serous ovarian cancer, predominantly originate from the fimbriated ends of the fallopian tube, whereas low-grade serous, clear cell, endometrioid and mucinous EOCs are thought to originate from other tissues. Despite recognized genetic susceptibilities for the disease, no effective screening is available and late-stage diagnosis remains common. Known genetic susceptibilities are addressed by risk reduction surgery including removal of both fallopian tubes and both ovaries. Management is predominantly based on adequate surgery and chemotherapy with carboplatin and paclitaxel, with the addition of anti-angiogenic therapy as indicated. The incorporation of poly(ADP-ribose) polymerase inhibitors into first-line therapy has considerably altered outcomes in some women with EOC who have defective homologous recombination DNA repair, including in those with BRCA1 and/or BRCA2 mutations. Other molecular characteristics are important in distinct types of EOC, but the use of matched targeted therapies remains under investigation, as does the role of immunotherapy for EOC, for which trial data have been disappointing to date. Translationally enriched clinical trials will be important to further explore and validate accurate biomarkers to better guide clinical care.