title: Emerging therapeutic targets in endometrial cancer.
abstract: Endometrial cancer comprises a heterogeneous group of tumors, with distinct risk factors, clinical presentation, histopathological features and molecular characteristics. Currently, treatment of metastatic or recurrent disease is based on conventional chemotherapy combination regimens. Advances in the understanding of the molecular pathology of the two types of endometrial carcinoma--type I (endometrioid) and type II (non-endometrioid)--have underpinned the first steps in the development and testing of targeted therapies. Of the potential therapeutic targets identified to date, clinical trials have only assessed the efficacy of inhibition of the EGFR, VEGFR and PI3K/PTEN/AKT/mTOR signaling pathways; responses to these targeted therapies were modest. Despite the striking molecular differences between type I and type II endometrial cancers, most clinical trials have not taken this diversity into account. The identification of activating mutations of kinases (for example PIK3CA and FGFR2) and loss of function of genes related to DNA repair (for example PTEN) may lead to more biology-driven clinical trials exploiting the concepts of oncogene addiction and synthetic lethality.
authors.affiliation: The Breakthrough Breast Cancer Research Center, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. konstantin.dedes@ usz.ch
authors.forename: Konstantin J
authors.initials: KJ
authors.lastname: Dedes
authors.forename: Daniel
authors.initials: D
authors.lastname: Wetterskog
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins