title: The mTOR protein as a target in thyroid cancer.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) protein is a downstream effector of the phosphatidilinositol-3 kinase (PI3K)/Akt pathway, which regulates not only cell proliferation and viability, but also iodide uptake in thyroid cells. Genetic alterations in the PI3K/Akt/mTOR pathway are common during thyroid cancer progression, and thus, these proteins are attractive targets for cancer therapy. So far, specific mTOR inhibitors, such as rapamycin analogs, have been developed and studied as anti-cancer agents.
  
  
  METHODS
  This review discusses evidence that justifies the potential use of mTOR signaling pathway inhibitors as therapeutic agents for thyroid cancer.
  
  
  CONCLUSIONS
  In the near future, mTOR-targeted drugs might represent a new approach for the therapy of thyroid cancer patients; rapamycin analogs have already been developed and are currently being clinically tested. Besides the antiproliferative action of mTOR inhibition, the stimulatory effect on thyroid iodide uptake can also be useful in the treatment of recurrent thyroid cancer. Therefore, if rapamycin analogs are able to increase iodide uptake in thyroid cancer, either alone or in combination with other agents, this will represent a new approach for the treatment of thyroid cancer, which may possibly improve the treatment of patients in which radioiodine therapy is not effective.
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, CCS - Bloco G - Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brasil.
authors.forename: Elaine Cristina Lima de
authors.initials: EC
authors.lastname: Souza
authors.forename: Andrea Claudia Freitas
authors.initials: AC
authors.lastname: Ferreira
authors.forename: Denise Pires de
authors.initials: DP
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007454:Iodides / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007454:Iodides; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus