Updates and emerging therapies for rare epithelial ovarian cancers: One size no longer fits all

Epithelial ovarian carcinoma consists of not one, but several, entities. A number of subtypes exist, including high-grade and low-grade serous carcinomas, clear cell, endometrioid carcinoma and mucinous carcinoma. Historically, women with epithelial ovarian cancer have been treated similarly and “lumped” in the same cooperative group treatment trials, irrespective of their tumor subtype. Recently, however, differences in epidemiology, tumor biology, tumor marker expression and treatment responses have been elucidated among the histologic subtypes, with a clear distinction emerging between the Type I, lower grade tumors and Type 2, higher grade epithelial malignancies. A mounting body of research demonstrates that a “one-size-fits-all” treatment approach to epithelial ovarian tumors is no longer relevant, especially for the Type I subtypes. Indeed, with the exception of high-grade serous carcinoma, most other epithelial subtypes exhibit some degree of chemotherapy resistance, rendering treatment problematic, especially in the setting of advanced disease. This review summarizes the genetic, molecular, and clinical differences of the more rare, but clinically important, Type I epithelial ovarian tumors. Additionally, a critical appraisal of both historical and contemporary treatment approaches and the rationale for targeted therapies are emphasized.