PDF(Pubmed)
Abstract：
Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.
摘要：
多发性骨髓瘤(MM),最终分化的浆细胞癌，是第二大最常见的血液恶性肿瘤，并且由于耐药性的不可避免的发展而无法治愈。强烈的蛋白质合成是MM细胞的独特特征，支持克隆免疫球蛋白或游离轻链的大规模生产。哺乳动物雷帕霉素靶蛋白（mTOR）激酶被认为是重要细胞过程的主要调节因子。包括调节代谢和蛋白质合成，可以在两个多蛋白复合物中找到，mTORC1和mTORC2。这些复合物的失调与几种类型的癌症有关，包括MM。由于mTOR已被证明在大部分MM患者中异常激活，并在刺激MM细胞存活和对几种现有疗法的抵抗中发挥作用，了解mTOR复合物的调节和功能对于开发更有效的治疗策略至关重要.这篇综述提供了mTOR通路的一般概述，讨论与mTOR复合物的结构和调控相关的关键发现和最新见解。此外,我们重点介绍了mTOR参与蛋白质合成的机制方面的发现,并深入研究了mTOR介导的在MM中发生的过程.最后,我们总结了针对MM中mTOR复合物的药物的进展和当前挑战。
