title: Endometrial cancer-targeted therapies myth or reality? Review of current targeted treatments.
abstract: Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries and its incidence is increasing related to obesity. EC is divided into histologic subtypes, most frequently endometrioid adenocarcinoma. Options for treatment of advanced or persistent disease remain limited, and survival has not changed in the last decade. No targeted therapy beyond hormonal therapy is approved for EC. Though hormonal therapy has been a 'standard' for four decades, prediction of its efficacy with receptor evaluation or understanding mechanisms of resistance remain important challenges. The clinical impact of deregulation of different pathways such as phosphatidylinositide 3-kinase, HER or MAPK warrant further investigation to use in a prognostic or predictive manner. The cell cycle and DNA repair pathways constitute potential targets for the development of precision therapies. Targeting the microenvironment and more recently immune infiltration are promising areas. Advances in the understanding of cell biology have allowed EC to be divided into multiple diseases that respond differently to targeted therapy. Translational clinical trials that link biology with precision targeted therapy are key to improve outcome and will require careful analysis or identification of potential biomarkers in early phase studies and validation in randomised trials. This approach requires collaborative efforts to achieve meaningful improvement in the prognosis of women with EC. This review aims to summarise the latest published trials on targeted therapies in EC and propose future directions.
authors.affiliation: Drug Development Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lheureux
authors.affiliation: Drug Development Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada. Electronic address: amit.oza@uhn.ca.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008687:Metformin / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D008687:Metformin; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Clinical trials; Endometrial cancer; Hormonal therapy; Targeted therapy