title: New Targeted Agents in Endometrial Cancer: Are We Really Making Progress?
abstract: Endometrial cancer is the most common gynecological malignancy in Europe and North America. Metastatic and recurrent disease is generally incurable with poor prognosis. Recent advances in molecular profiling of endometrial cancer have elucidated four distinct molecular subtypes with different biology and prognosis which should facilitate the development of treatments tailored to disease-specific subgroups. To date, some molecular-targeted agents have shown interesting clinical activity in the recurrent setting, but no targeted therapies are approved for endometrial cancer. Novel pan-PI3K, AKT, and dual PI3K-mTOR inhibitors are being investigated with early signs of activity, but there are concerns about tolerability and toxicity in this often elderly patient population with comorbidities. The development of anti-angiogenic therapies, PARP inhibitors, and immunotherapies, alone or in combinations, appear to be promising strategies. This paper will describe the current evidence supporting the efficacy of molecular-targeted agents already tested in the treatment of metastatic and recurrent EC, and provide some insights on emerging data related to novel-targeted therapies.
authors.affiliation: Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Rodriguez-Freixinos
authors.affiliation: Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Karakasis
authors.affiliation: Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada. amit.oza@uhn.ca.|Princess Margaret Cancer Center, Bras Family Drug Development Program, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. amit.oza@uhn.ca.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D003131:Combined Modality Therapy; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Cancer; Chemotherapy; Endometrial cancer; Endometrium; Molecular targets; Targeted therapy