Blood malignancies remain a therapeutic challenge despite the development of numerous treatment strategies. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway plays a central role in regulating many cellular functions, including cell cycle, proliferation, quiescence, and longevity. Therefore, dysregulation of this pathway is a characteristic feature of carcinogenesis. Increased activation of PI3K/Akt/mTOR signaling enhances proliferation, growth, and resistance to chemo- and immunotherapy in cancer cells. Overactivation of the pathway has been found in various types of cancer, including acute and chronic leukemia. Inhibitors of the PI3K/Akt/mTOR pathway have been used in leukemia treatment since 2014, and some of them have improved treatment outcomes in clinical trials. Recently, new inhibitors of PI3K/Akt/mTOR signaling have been developed and tested both in preclinical and clinical models. In this review, we outline the role of the PI3K/Akt/mTOR signaling pathway in blood malignancies’ cells and gather information on the inhibitors of this pathway that might provide a novel therapeutic opportunity against leukemia.
尽管已发展出多种治疗策略，血液恶性肿瘤仍是治疗上的难题。磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路在调控细胞周期、增殖、静息及寿命等多种细胞功能中发挥核心作用，因此该通路的失调是致癌过程的典型特征。PI3K/Akt/mTOR信号通路的过度激活会增强癌细胞的增殖、生长及对化疗与免疫治疗的耐药性。该通路的异常活化已在包括急慢性白血病在内的多种癌症中被发现。自2014年以来，PI3K/Akt/mTOR通路抑制剂已应用于白血病治疗，其中部分药物在临床试验中显示出改善疗效的作用。近期，针对该信号通路的新型抑制剂已在临床前及临床模型中完成研发与验证。本综述系统阐述了PI3K/Akt/mTOR信号通路在血液恶性肿瘤细胞中的作用机制，并汇总了该通路抑制剂的相关研究进展，这些抑制剂可能为白血病治疗提供新的治疗策略。
PI3K/Akt/mTOR Signaling Pathway in Blood Malignancies—New Therapeutic Possibilities
肿瘤(癌症)患者之家