title: A Review of mTOR Pathway Inhibitors in Gynecologic Cancer.
abstract: The treatment of advanced gynecologic cancers remains palliative in most of cases. Although systemic treatment has entered into the era of targeted drugs the antitumor efficacies of current therapies are still limited. In this context there is a great need for more active treatment and rationally designed targeted therapies. The PI3K/AKT/mTOR is a signaling pathway in mammal cells that coordinates important cell activities. It has a critical function in the survival, growth, and proliferation of malignant cells and was object of important research in the last two decades. The mTOR pathway emerges as an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli and, through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including endometrial, cervical, and ovarian cancers. The present study reviewed the available evidence regarding the potential impact of some mTOR pathway inhibitors in the treatment of gynecological cancer. Few advances in medical management have occurred in recent years in the treatment of advanced or recurrent gynecological malignancies, and a poor prognosis remains. Rationally designed molecularly targeted therapy is an emerging and important option in this setting; then more investigation in PI3K/AKT/mTOR pathway-targeted therapies is warranted.
authors.affiliation: Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Andréia Cristina
authors.identifier: 0000-0002-1201-4333
authors.initials: AC
authors.lastname: de Melo
authors.affiliation: Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Paulino
authors.affiliation: Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Álvaro Henrique Ingles
authors.initials: ÁH
authors.lastname: Garces
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases