Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.
Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.
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哺乳动物雷帕霉素靶点(MTOR)复合体在膀胱癌进展和治疗中的新作用。
DOI：
10.3390/cancers14061555
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发表时间：
2022-03-18
期刊：
影响因子：
5.2
通讯作者：
Hansel DE
中科院分区：
文献类型：
--
作者：
Huan J;Grivas P;Birch J;Hansel DE
哺乳动物雷帕霉素靶蛋白（mTOR）途径响应于生长因子、营养物和细胞能量状态促进细胞生长和代谢。mTOR通路的失调和突变可促进肿瘤的发生和进展。在大约70%的尿路上皮癌（UC）中发现了mTOR通路异常。本文综述了mTOR通路的最新研究进展，强调了mTOR通路在UC中的作用，并探讨了mTOR通路作为UC治疗靶点的潜力。该综述还探讨了目前针对mTOR通路的临床前研究和临床试验，并得出结论，未来的研究方向可以更有力地定义和靶向膀胱癌中的异常mTOR活性。哺乳动物雷帕霉素靶蛋白（mTOR）通路调节重要的细胞功能。该途径的异常激活，无论是通过生长因子的上游激活、抑制控制的丧失还是分子改变，都可以促进癌症的生长和进展。膀胱癌在大约70%的尿路上皮癌中显示出高水平的mTOR活性，表明该途径在这种癌症中起关键作用。mTOR信号传导通过磷脂酰肌醇3激酶（PI3 K）和蛋白激酶B（AKT）的上游活化而起始，并导致mTOR复合物1（mTORC 1）或mTOR复合物2（mTORC 2）的活化。虽然这些复合物共有几种关键蛋白质组分，但其复合物组成的独特差异显著改变了mTOR活性的功能和下游细胞靶点。虽然大量的工作已经进入膀胱癌中mTOR通路的分子改变的分析，但迄今为止，这在尿路上皮癌的mTOR靶向治疗方法中尚未产生显著的益处。关于膀胱癌中mTOR复合物的信号转导会聚的新发现可能会对这种侵袭性疾病的生物学和靶向产生独特的见解。在这篇综述中，我们强调了mTOR信号在尿路上皮癌中的功能意义及其对未来治疗的潜在影响。
The mammalian target of rapamycin (mTOR) pathway promotes cell growth and metabolism in response to growth factors, nutrients, and cellular energy status. Dysregulation and mutation of the mTOR pathway can contribute to tumor initiation and progression. mTOR pathway abnormalities have been found in approximately 70% of urothelial carcinomas (UCs). This review summarizes recent advances in knowledge of the mTOR pathway, highlights the role of the mTOR pathway in UC, and explores the potential of the mTOR pathway as a therapeutic target in UC. This review also explores current preclinical studies and clinical trials targeting the mTOR pathway, and concludes with future directions of research that could more robustly define and target aberrant mTOR activity in bladder cancer. The mammalian target of rapamycin (mTOR) pathway regulates important cellular functions. Aberrant activation of this pathway, either through upstream activation by growth factors, loss of inhibitory controls, or molecular alterations, can enhance cancer growth and progression. Bladder cancer shows high levels of mTOR activity in approximately 70% of urothelial carcinomas, suggesting a key role for this pathway in this cancer. mTOR signaling initiates through upstream activation of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) and results in activation of either mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2). While these complexes share several key protein components, unique differences in their complex composition dramatically alter the function and downstream cellular targets of mTOR activity. While significant work has gone into analysis of molecular alterations of the mTOR pathway in bladder cancer, this has not yielded significant benefit in mTOR-targeted therapy approaches in urothelial carcinoma to date. New discoveries regarding signaling convergence onto mTOR complexes in bladder cancer could yield unique insights the biology and targeting of this aggressive disease. In this review, we highlight the functional significance of mTOR signaling in urothelial carcinoma and its potential impact on future therapy implications.
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DOI：
10.3233/blc-160090
发表时间：
2017-04-27
期刊：
Bladder cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Bachir BG;Souhami L;Mansure JJ;Cury F;Vanhuyse M;Brimo F;Aprikian AG;Tanguay S;Sturgeon J;Kassouf W
通讯作者：
Kassouf W
DOI：
10.1016/j.urolonc.2013.06.002
发表时间：
2014-04
期刊：
Urologic oncology
影响因子：
--
作者：
Becker MN;Wu KJ;Marlow LA;Kreinest PA;Vonroemeling CA;Copland JA;Williams CR
通讯作者：
Williams CR
影响因子：
64.8
作者：
Bernardi, Rosa;Guernah, Ilhem;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
5
作者：
Ashrafizadeh, Milad;Zarrabi, Ali;Najafi, Masoud
通讯作者：
Najafi, Masoud