Rapamycin and mTORC1 inhibition in the mouse: skin cancer prevention.
Rapamycin and mTORC1 inhibition in the mouse: skin cancer prevention.
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DOI：
10.1158/1940-6207.capr-11-0266
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Kopelovich L
中科院分区：
文献类型：
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作者：
Athar M;Kopelovich L
雷帕霉素的治疗和预防作用包括降低非黑色素瘤皮肤癌（NMSC）的风险。在本期杂志（从第XXX页开始）中，切克利等人报告称，雷帕霉素抑制小鼠表皮中的雷帕霉素靶蛋白（mTOR）复合物1，从而抑制由十四酰佛波醇 - 13 - 乙酸酯（TPA）介导的肿瘤促进作用，同时具有很强的抗炎效果。雷帕霉素是一种免疫抑制药物，用于预防器官移植受者的移植物排斥反应，并降低该人群中非黑色素瘤皮肤癌和卡波西肉瘤的风险，尽管其机制不同于免疫抑制。未来重要的研究方向包括确定雷帕霉素/雷帕霉素类似物敏感性或耐药性的分子预测因子（例如可能是PI3K通路改变和KRAS突变）以及联合非雷帕霉素类似物、靶向mTOR的方法，所有这些都应提高疗效并将毒性降至最低。
Therapeutic and preventive effects of rapamycin include reduced risk of non-melanoma skin cancer (NMSC). In this issue of the journal (beginning on page XXX), Checkley et al. report that rapamycin inhibits mammalian target of rapamycin (mTOR) complex 1 in murine epidermis, thereby inhibiting tumor promotion mediated by tetradecanoyl phorbol-13 acetate (TPA) in association with a strong anti-inflammatory effect. Rapamycin is an immunosuppressive drug for preventing graft rejection in organ transplant recipients and reduces the risk of NMSC and Kaposi’s sarcoma in this population, albeit by mechanisms distinct from immunosuppression. Important future directions include identifying molecular predictors of rapamycin/rapalog sensitivity or resistance (potentially, for example, PI3K pathway alterations and KRAS mutations) and combined non-rapalog, mTOR-targeting approaches, all of which should increase efficacy and minimize toxicity.