mTOR抑制剂放疗增敏的研究进展

Research on mTOR inhibitors used in radio-sensitization

放疗是肿瘤的重要治疗手段之一,仍有部分患者在接受放疗后存在复发或抗拒。哺乳动物雷帕霉素靶蛋白(mamma-lian target of rapamycin,mTOR)是PI3K/AKT信号通路的主要效应分子,分为mTORC1和mTORC2,对细胞生长及增殖、细胞周期进展及蛋白翻译等均有重要调节作用。mTOR异常表达与肿瘤发生及治疗反应密切相关。肿瘤的放疗敏感性与"4R"效应有关。mTOR抑制剂可通过影响细胞周期进展、DNA损伤修复及抗血管形成等多种途径发挥放疗增敏作用。初期研究证实依维莫司具有放疗增敏作用并且毒性可耐受。应用mTOR抑制剂后不同细胞及个体反应不同,可能与基因表达状态有关,需进一步研究证实。

Radiotherapy is important for cancer treatment. However, some patients still experience relapse and exhibit radiation resistance. Mammalian target of rapamycin （mTOR） is the main effector molecule in PI3K/AKT signaling. This molecule is found in two structurally and functionally distinct multi-protein complexes known as the mTOR complex 1 and mTOR complex 2. The mTOR signaling pathway controls the growth, proliferation, survival, and apoptosis of cancer cells. This pathway is closely related to tumori-genesis and treatment response, and is used in sensitizing radiotherapy. mTOR inhibitors regulate radio-sensitization through multiple mechanisms, including cell cycle alterations, DNA repair modulation, and tumor hypoxia reduction. Preclinical studies showed that mTOR inhibitors with tolerable toxicity may be used as an effective modality to overcome radio-resistant tumors. Responses to mTOR inhibitors vary depending on the cell lines. Molecular markers can be used to select suitable patients. Further studies are needed to com-pletely understand the use of mTOR inhibitors in radio-sensitization.