Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, CCS - Bloco G - Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brasil.
Expert Opin Ther Targets. 2011 Sep;15(9):1099-112. doi: 10.1517/14728222.2011.594044. Epub 2011 Jun 25.
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.
This review discusses evidence that justifies the potential use of mTOR signaling pathway inhibitors as therapeutic agents for thyroid cancer.
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.
哺乳动物雷帕霉素靶蛋白（mTOR）是磷脂酰肌醇-3 激酶（PI3K）/ Akt 通路的下游效应物，它不仅调节细胞增殖和活力，还调节甲状腺细胞对碘的摄取。PI3K/Akt/mTOR 通路的遗传改变在甲状腺癌进展过程中很常见，因此，这些蛋白是癌症治疗的有吸引力的靶点。到目前为止，已经开发并研究了特定的 mTOR 抑制剂，如雷帕霉素类似物，作为抗癌药物。
这篇综述讨论了支持将 mTOR 信号通路抑制剂用作甲状腺癌治疗剂的潜在用途的证据。
在不久的将来，mTOR 靶向药物可能代表甲状腺癌患者治疗的新方法；雷帕霉素类似物已经开发出来，目前正在进行临床测试。除了 mTOR 抑制的抗增殖作用外，对甲状腺碘摄取的刺激作用在复发性甲状腺癌的治疗中也可能有用。因此，如果雷帕霉素类似物能够单独或与其他药物联合增加甲状腺癌中的碘摄取，这将代表治疗甲状腺癌的一种新方法，这可能会改善对放射性碘治疗无效的患者的治疗。
