The disparate origins of ovarian cancers: pathogenesis and prevention strategies

Historically, one of the main reasons why the biology and evolution of common ovarian cancers have been so difficult to understand is because most tumour cells do not phenotypically resemble any normal cells in the ovary. For high-grade serous carcinoma (HGSC), the most common ovarian cancer, no credible histological precursor lesion had been identified until 15 years ago, and the majority of mucinous carcinomas of the ovary are metastases from other organs1. For other ovarian tumours, for which a precursor lesion has been identified, such as endometriosis for clear cell carcinoma (CCC) and endometrioid carcinoma (EC), it is still not known how the precursor develops2. These and other issues have substantially hampered our understanding of the origin of ovarian cancers and their pathogenesis, and thereby limited our ability to study them in experimental systems. Furthermore, the realization that the most common ovarian cancer types arise from cells that are not normally located in the ovary challenges the concept of what a 'true' ovarian cancer is.