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中文摘要：
哺乳动物雷帕霉素靶蛋白（mTOR）是PI3K/Akt/mTOR等多种信号通路的下游分子,在细胞增殖、分化、转移和存活中发挥重要作用,已成为癌症治疗的一个重要靶标。传统的mTOR抑制剂主要是雷帕霉素及其衍生物,能特异性抑制mTORC1,但在部分癌症临床治疗中未达到预期疗效,且易产生耐药性。第二代mTOR抑制剂即双重或多重mTOR抑制剂能与mTOR的催化位点竞争ATP,高度选择性地抑制mTORC1和mTORC2,比单靶点mTOR抑制剂具有更大的治疗优势。此外,某些天然来源产物也具有对mTOR的抑制作用,且毒性、副作用更小。综述近几年有关mTOR及其抑制剂在抗肿瘤方面的研究进展。
英文摘要：
As a downstream molecule of various pathways such as PI3K/Akt/mTOR pathway, mTOR plays important roles in cell proliferation, differentiation, metastasis and survival, emerging as a key protein target of anticancer drugs. Traditional mTOR inhibitors, rapamycin and its analogs, can effectively inhibit mTORC1, but suffer from limited clinical efficacy and easy development of drug resistance. The second generation mTOR inhibitors are dual or multiple mTOR inhibitors that can compete with the catalytic site of mTOR for ATP and inhibit both mTORC1 and mTORC2 with a high selectivity, showing advantages over single inhibitors. Furthermore, some natural compounds have been found to inhibit mTOR with low toxicity and less side effects. In this paper, we reviewed the latest research in mTOR and its inhibitors as anticancer drugs.
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