Balsat Marie, Cornillon Jérôme
Institut de cancérologie de la Loire, service d'hématologie clinique, Saint-Priest-en-Jarez, France.
Bull Cancer. 2011 Aug;98(8):935-43. doi: 10.1684/bdc.2011.1413.
Mammalian target of rapamycyin (mTOR) is a downstream serine/threonine kinase of the PI3K/AKT pathway that integrates signals from the microenvironment such as cytokines, growth factors, and nutriments to regulate multiple cellular processes, including mRNA translation, autophagy, metabolism, growth and survival. mTOR operates in two distinct multi-protein complexes: mTORC1 and mTORC2; sharing mTOR kinase as a common catalytic subunit, mTORC1 controls cell growth and mTORC2 modulates cell survival and drug resistance. mTOR signalling pathway has been found to be deregulated in many haematological malignancies, and has been designed as an attractive anti-tumor target. Thereby, mTOR inhibition with rapamycin (sirolimus) or its derivates (rapalogs) represents promising treatments, either alone or in combination with strategies to target other pathways that may overcome resistance. At present time, numerous clinical trials with mTOR inhibitors are ongoing for treatment of haematological diseases with modest or promising results. The aim of this review is to present the rationale for using mTOR inhibitors in haematology, first via biological explanations and secondly, by focusing on each haematological malignancies with new perspective of treatment.
雷帕霉素哺乳动物靶点（mTOR）是PI3K/AKT信号通路下游的丝氨酸/苏氨酸激酶，它整合来自细胞因子、生长因子和营养物质等微环境的信号，以调节多种细胞过程，包括mRNA翻译、自噬、代谢、生长和存活。mTOR存在于两种不同的多蛋白复合物中：mTORC1和mTORC2；mTORC1和mTORC2共享mTOR激酶作为共同的催化亚基，mTORC1控制细胞生长，mTORC2调节细胞存活和耐药性。已发现mTOR信号通路在许多血液系统恶性肿瘤中失调，并被设计为一个有吸引力的抗肿瘤靶点。因此，用雷帕霉素（西罗莫司）或其衍生物（雷帕霉素类似物）抑制mTOR代表着有前景的治疗方法，无论是单独使用还是与靶向其他可能克服耐药性的信号通路的策略联合使用。目前，有许多使用mTOR抑制剂治疗血液系统疾病的临床试验正在进行，取得了一定或有前景的结果。这篇综述的目的是阐述在血液学中使用mTOR抑制剂的理论依据，首先通过生物学解释，其次通过从新的治疗角度关注每种血液系统恶性肿瘤来进行阐述。
