Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway

In the majority of cases, endometrial cancer is localized and highly curable through surgery and adjuvant radiotherapy. However, for patients with advanced or metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic chemotherapy or hormonal therapy can cause significant toxicities including chemotherapy-related gastrointestinal, neurologic, and immunosuppressive toxicities and hormone-related hypertension, increased blood sugar, thrombosis, and pulmonary emboli. In addition, these therapies rarely lead to sustained disease control. Novel therapies with greater efficacy and reduced toxicity are needed. Recent progress in the identification of genetic abnormalities in cell signaling proteins has spurred the development of targeted agents for the treatment of patients with endometrial cancer. The fibroblast growth factor receptor (FGFR) pathway is one of several signaling pathways that have been implicated in the pathogenesis and progression of endometrial cancer. The activity of novel FGFR-targeted agents in preclinical endometrial cancer models and clinical trials will be reviewed.