title: Targeting angiogenesis in endometrial cancer - new agents for tailored treatments.
abstract: BACKGROUND
  Endometrial carcinoma represents the most frequent gynecologic tumor in developed countries. The majority of women presents with low-grade tumors but a significant subset of women experience recurrence and do not survive their disease. Patients with stage III/ IV or recurrent endometrial cancer have a poor prognosis. Identification of active and tolerable new targeted agents versus specific molecular targets is a priority objective. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer and in particular endometrial cancer.
  
  
  METHODS
  In this review, the authors highlight the main angiogenetic molecular pathways and the anti-angiogenic agents in Phase II clinical trials for endometrial cancer treatment. The authors focus on reports from recent years on angiogenesis inhibitors used in endometrial cancer, including anti- vascular endothelial growth factor (VEGF) monoclonal antibodies (bevacizumab and aflibercept), mammalian target of rapamycin inhibitors (mTORi) (everolimus, temsirolimus and ridaforolimus), PI3 K inhibitors (BKM120), tyrosine kinase inhibitors (brivanib, sunitinib, dovitinib and nintedanib) and thalidomide.
  
  
  CONCLUSIONS
  These anti-angiogenic drugs, while used either alone or in combination with chemotherapy, have presented mixed results in treating endometrial cancer patients. Challenges for the future include the identification of new pathways, early identification and overcoming resistance and the use of these molecules in combination with old and new chemotherapeutic and targeted agents.
authors.affiliation: a Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit , Istituto Chirurgico Ortopedico Traumatologico , 04100 Latina , Italy.
authors.forename: Anselmo
authors.initials: A
authors.lastname: Papa
authors.affiliation: a Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit , Istituto Chirurgico Ortopedico Traumatologico , 04100 Latina , Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zaccarelli
authors.affiliation: a Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit , Istituto Chirurgico Ortopedico Traumatologico , 04100 Latina , Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Caruso
authors.affiliation: b Division of Medical Oncology B , Regina Elena National Cancer Institute , 00144 Rome , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: c Department of Gynecological, Obstetrical and Urologic Sciences , "Sapienza" University of Rome , 00186 Rome , Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Benedetti Panici
authors.affiliation: c Department of Gynecological, Obstetrical and Urologic Sciences , "Sapienza" University of Rome , 00186 Rome , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tomao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents
keywords: angiogenesis; endometrial cancer; monoclonal antibodies; small molecules; target therapies