3-磷脂酰肌醇依赖的蛋白激酶1（PDK1）被认为是调节AGC激酶家族成员AKT，SGK，PLK，S6K和RSK的主要激酶。虽然自磷酸化调节PDK1的活性，但累积的证据表明PDK1还受到许多其他机制的调控，包括S6K介导的磷酸化和E3连接酶SPOP介导的泛素化和降解。这些上游调节因子或下游信号的失调与癌症的发展有关，因为PDK1调节细胞生长、转移、侵袭、凋亡和生存时间。与此同时，PDK1在许多癌症中也表达过度，而PDK1的抑制则减小细胞大小，抑制肿瘤生长和进展。更重要的是，PDK1还调节肿瘤微环境，并且显著影响肿瘤免疫治疗。总之，本文全面总结了PDK1的下游信号、上游调控因子、小鼠模型、抑制剂、肿瘤微环境和临床治疗，并强调PDK1作为潜在的癌症治疗靶点。版权所有 © 2023。由Elsevier B.V.出版。

3-phosphoinositide-dependent protein kinase 1 (PDK1) is considered as master kinase regulating AGC kinase family members such as AKT, SGK, PLK, S6K and RSK. Although autophosphorylation regulates PDK1 activity, accumulating evidence suggests that PDK1 is manipulated by many other mechanisms, including S6K-mediated phosphorylation, and the E3 ligase SPOP-mediated ubiquitination and degradation. Dysregulation of these upstream regulators or downstream signals involves in cancer development, as PDK1 regulating cell growth, metastasis, invasion, apoptosis and survival time. Meanwhile, overexpression of PDK1 is also exposed in a plethora of cancers, whereas inhibition of PDK1 reduces cell size and inhibits tumor growth and progression. More importantly, PDK1 also modulates the tumor microenvironments and markedly influences tumor immunotherapies. In summary, here we comprehensively summarize the downstream signals, upstream regulators, mouse models, inhibitors, tumor microenvironment and clinical treatments for PDK1, and highlight PDK1 as a potential cancer therapeutic target.Copyright © 2023. Published by Elsevier B.V.