Liu Yanyan, Sun Qiu, Wei Xiawei
Laboratory of Aging Research and Cancer Drug Target, Department of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan, People's Republic of China.
West China Medical Publishers, West China Hospital, Sichuan University, Chengdu, China.
Expert Opin Ther Targets. 2024 Mar;28(3):221-232. doi: 10.1080/14728222.2024.2342522. Epub 2024 May 21.
The PI3K/AKT/mTOR signaling pathway is an important signaling pathway in eukaryotic cells that is activated in a variety of cancers and is also associated with treatment resistance. This signaling pathway is an important target for anticancer therapy and holds great promise for research. At the same time PI3K inhibitors have a general problem that they have unavoidable toxic side effects.
This review provides an explanation of the role of PI3K in the development and progression of cancer, including several important mutations, and a table listing the cancers caused by these mutations. We discuss the current landscape of PI3K inhibitors in preclinical and clinical trials, address the mechanisms of resistance to PI3K inhibition along with their associated toxic effects, and highlight significant advancements in preclinical research of this field. Furthermore, based on our study and comprehension of PI3K, we provide a recapitulation of the key lessons learned from the research process and propose potential measures for improvement that could prove valuable.
The PI3K pathway is a biological pathway of great potential value. However, the reduction of its toxic side effects and combination therapies need to be further investigated.
PI3K/AKT/mTOR信号通路是真核细胞中的一条重要信号通路，在多种癌症中被激活，且与治疗耐药性相关。该信号通路是抗癌治疗的重要靶点，具有巨大的研究前景。同时，PI3K抑制剂存在一个普遍问题，即它们具有不可避免的毒副作用。
本综述解释了PI3K在癌症发生和发展中的作用，包括几种重要的突变，并列出了由这些突变引起的癌症的表格。我们讨论了PI3K抑制剂在临床前和临床试验中的现状，探讨了对PI3K抑制的耐药机制及其相关的毒性作用，并强调了该领域临床前研究的重大进展。此外，基于我们对PI3K的研究和理解，我们总结了研究过程中的关键经验教训，并提出了可能有价值的潜在改进措施。
PI3K通路是一条具有巨大潜在价值的生物学通路。然而，其毒副作用的降低和联合治疗仍需进一步研究。
