Low-grade serous carcinoma of the ovary or peritoneum.

Over the past decade, the strategy for clinical trial design in making progress against epithelial cancers of the ovary/peritoneum/fallopian tube has changed dramatically. The NRG (GOG) Rare Tumor Committee has been a leader in this transformation. No longer does 'one size fit all'. Rather, separate clinical trials for rare subtypes have been developed and, in some cases, completed. An enhanced understanding of their pathologic diagnosis, molecular biology, and clinical behavior has galvanized this change. Low-grade serous carcinoma may occur de novo or following an initial diagnosis of serous tumor of low malignant potential. It is characterized by young age at diagnosis, relative chemoresistance, and prolonged survival compared with high-grade serous carcinoma. Historically, conventional chemotherapy has demonstrated very limited activity in this subtype. Hormonal therapy may provide benefit in this subtype. Preclinical studies have identified and elucidated genes and pathways-MAP kinase pathway, IGF1-R, the angiogenesis pathway, and possibly, the PI3K/AKT/mTOR pathway in low-grade serous carcinoma. To date, clinical evidence supports the activity of MEK and BRAF inhibitors and bevacizumab. Further pursuit of targeted therapy trials is clearly warranted.