Exploiting the mammalian target of rapamycin pathway in hematologic malignancies
Exploiting the mammalian target of rapamycin pathway in hematologic malignancies
复制标题
DOI：
10.1097/moh.0b013e3282f3deaa
复制
发表时间：
2008-03-01
影响因子：
3.2
通讯作者：
Platanias, Leonidas C.
中科院分区：
文献类型：
--
作者：
Altman, Jessica K.;Platanias, Leonidas C.
综述目的本综述批判性地评估了阐明哺乳动物雷帕霉素靶点在血液恶性肿瘤发病机制中的作用以及靶向该信号通路治疗此类恶性肿瘤的潜力的最新研究进展。最新发现哺乳动物雷帕霉素靶点是一种高度保守的丝氨酸/苏氨酸蛋白激酶，控制mRNA翻译的起始、细胞周期进展和细胞增殖。最近，在哺乳动物雷帕霉素靶点及其效应物的细胞信号传导研究方面取得了巨大进展，以及对血液恶性肿瘤中哺乳动物雷帕霉素靶点通路异常激活的更好理解，激发了人们对针对该通路的抑制剂的临床开发的极大兴趣。目前正在针对各种血液恶性肿瘤开展大量使用哺乳动物雷帕霉素抑制剂靶点的临床试验。此类试验是临床前工作的直接延伸，证实抑制该途径可在体外和体内阻断细胞增殖和/或诱导细胞凋亡。总结雷帕霉素途径的哺乳动物靶标在血液系统恶性肿瘤中的作用引起了人们相当大的兴趣，具有重大的临床/转化相关性。在这里，总结了我们对雷帕霉素途径哺乳动物靶标的功能作用及其在血液恶性肿瘤中的失调的理解，并讨论了由此产生的临床/转化工作。
Purpose of review This review critically assesses recent research advances in elucidating the role of the mammalian target of rapamycin pathway in the pathogenesis of hematologic malignancies and the potential of targeting this signaling pathway to treat such malignancies.Recent findings Mammalian target of rapamycin is a highly conserved serine/threonine protein kinase that controls initiation of mRNA translation, cell cycle progression, and cellular proliferation. Recent dramatic advances in research into cellular signaling by mammalian target of rapamycin and its effectors, and better understanding of aberrant activation of mammalian target of rapamycin pathways in hematologic malignancies have stimulated considerable interest in the clinical development of inhibitors that target this pathway. Numerous clinical trials using mammalian target of rapamycin inhibitors are ongoing in various hematologic malignancies. Such trials are direct extensions of preclinical work establishing that inhibition of this pathway blocks cell proliferation and/or induces apoptotic cell death, both in vitro and in vivo.Summary The role of the mammalian target of rapamycin pathway in hematologic malignancies is of considerable interest with major clinical/translational relevance. Here, our understanding of the functional roles of the mammalian target of rapamycin pathway and its deregulation in hematologic malignancies are summarized and resulting clinical/translational efforts discussed.