PI3K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application.

TLDR

Cancer stem cells are a tumor subpopulation with self‑renewal that drive initiation and propagation, and the PI3K/Akt/mTOR pathway is a master regulator linked to CSC biology. This review aims to delineate the role of PI3K/Akt/mTOR signaling components in CSC and evaluate small‑molecule inhibitors for clinical application. The authors systematically examine upstream and downstream signaling elements and catalogue inhibitor classes to assess therapeutic prospects. The evidence suggests that targeting PI3K/Akt/mTOR offers a promising strategy for developing CSC‑targeted drugs.

Abstract

Cancer stem cells (CSCs) are a subpopulation of tumor cells that possess unique self-renewal activity and mediate tumor initiation and propagation. The PI3K/Akt/mTOR signaling pathway can be considered as a master regulator for cancer. More and more recent studies have shown the links between PI3K/Akt/mTOR signaling pathway and CSC biology. Herein, we provide a comprehensive review on the role of signaling components upstream and downstream of PI3K/Akt/mTOR signaling in CSC. In addition, we also summarize various classes of small molecule inhibitors of PI3K/Akt/mTOR signaling pathway and their clinical potential in CSC. Overall, the current available data suggest that the PI3K/Akt/mTOR signaling pathway could be a promising target for development of CSC-target drugs.