Updates in therapy for uterine serous carcinoma

Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer with distinct molecular pathogenesis. This review summarizes the rationale behind current clinical approaches, as well as advances made in 2012 toward the elucidation of underlying pathway aberrations and development of targeted therapies that exploit these unique characteristics.

Within the last year, exome-wide analyses have highlighted key mutations to guide rational drug design. The PI3/AKT/mTOR pathway and regulators of cell cycle such as cyclin E/F-box proteins appear to be particularly important. Understanding the epithelial to mesenchymal transition may explain the aggressive pattern of spread frequently observed in this disease. There is heightened evidence for heritable syndromes in association with USC. Conflicting retrospective data continue to emerge regarding optimal therapy, especially for early-stage disease, although prospective studies are underway. Immunotherapies targeting Her2/Neu and vascular endothelial growth factor remain an area of active research. Upregulation of class III β-tubulin observed in paclitaxel-resistant disease may identify candidates for therapy with novel microtubule-stabilizing agents such as epothilones.

There is an expanding role for contemporary novel approaches in the treatment of USC. The results of clinical investigations using new target antigens, epothilones, and small molecule inhibitors are eagerly awaited.