磷脂酰肌醇3激酶-蛋白激酶B-哺乳动物雷帕霉素靶标信号通路抑制剂在抗肿瘤治疗中的研究进展

Research progress of phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signaling pathway inhibitors in anti-tumor therapy

磷脂酰肌醇3激酶(PI3K)-蛋白激酶B(Akt/PKB)-哺乳动物雷帕霉素靶标(mTOR)通路是各类肿瘤细胞内重要的信号转导通路之一,通过调控不同的下游分子,参与并调控包括增殖、凋亡在内的多种肿瘤细胞恶性生物学行为。随着PAM通路的组成及分子机制研究的深入,针对该通路不同位点的抑制剂逐渐进入临床试验阶段,并逐渐表现出作为肿瘤潜在治疗靶点的潜力。本文旨在对多种PAM通路抑制剂,以及这些药物与其他肿瘤治疗方式联合应用进行综述及展望。

The phosphoinositide 3-kinase(PI3K)-Akt/protein kinase B(PKB)-mammalian target of rapamycin(mTOR)pathway is one of the significant signal transduction pathways in various tumor cells.By regulating different downstream molecules,it participates in and regulates various malignant biological behaviors of tumor cells including proliferation and apoptosis.With the in-depth research on the composition and molecular mechanism of the PAM pathway,inhibitors targeting different sites of the pathway have gradually entered the stage of clinical trials,and have gradually shown their potential as tumor therapeutic targets.This article aims to review and prospect a variety of PAM pathway inhibitors,as well as the combination of these inhibitors with other tumor treatment modalities.