Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Shahid Babai Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Pathol Res Pract. 2022 Sep;237:154010. doi: 10.1016/j.prp.2022.154010. Epub 2022 Jul 3.
Cancer stem cells (CSCs) as a small subpopulation in tumor bulk are believed to initiate tumor formation and are responsible for the resistance to cancer therapy. The proliferation and differentiation of CSCs result in heterogeneity in a tumor which increases the chance of tumor survival and invasion. Many signaling pathways are abnormally activated or repressed in CSCs. Understanding these pathways and the metabolisms in CSCs may help targeted therapy in drug-resistant tumors. The PI3K/Akt/mTOR pathway is one of the major signaling pathways in CSCs involved in the maintenance of stemness, proliferation, differentiation, epithelial to mesenchymal transition (EMT), migration, and autophagy. Thus, suppressing the PI3K/Akt/mTOR pathway with inhibitors might be a promising strategy for targeted cancer therapy. Although the pathway is well-recognized and reviewed in tumor bulks, the functions in CSCs have not been well focused. Here, we reviewed the PI3K/Akt/mTOR signaling pathway and its functions in CSCs and addressed the potential therapeutic applications in drug-resistant tumors.
肿瘤干细胞（CSC）作为肿瘤块中的一小部分亚群，被认为能够引发肿瘤的形成，并对癌症治疗的耐药性负责。CSC 的增殖和分化导致肿瘤的异质性增加，从而增加了肿瘤存活和侵袭的机会。在 CSC 中，许多信号通路异常激活或受到抑制。了解这些通路和 CSC 中的代谢可能有助于耐药肿瘤的靶向治疗。PI3K/Akt/mTOR 通路是 CSC 中参与维持干性、增殖、分化、上皮间质转化（EMT）、迁移和自噬的主要信号通路之一。因此，用抑制剂抑制 PI3K/Akt/mTOR 通路可能是一种有前途的靶向癌症治疗策略。尽管该通路在肿瘤块中得到了很好的认识和研究，但在 CSC 中的功能尚未得到很好的关注。在这里，我们综述了 PI3K/Akt/mTOR 信号通路及其在 CSC 中的功能，并探讨了其在耐药肿瘤中的潜在治疗应用。
