Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Biochem Pharmacol. 2023 Nov;217:115842. doi: 10.1016/j.bcp.2023.115842. Epub 2023 Oct 5.
RAS/RAF/MEK/ERK signaling pathway is one of the most important pathways of Mitogen-activated protein kinases (MAPK), which widely participate in regulating cell proliferation, differentiation, apoptosis and signaling transduction. Autophagy is an essential mechanism that maintains cellular homeostasis by degrading aged and damaged organelles. Recently, some studies revealed RAS/RAF/MEK/ERK signaling pathway is closely related to autophagy regulation and has a dual effect in tumor cells. However, the specific mechanism by which RAS/RAF/MEK/ERK signaling pathway participates in autophagy regulation is not fully understood. This article provides a comprehensive review of the research progress with regard to the RAS/RAF/MEK/ERK signaling pathway and autophagy, as well as their interplay in cancer therapy. The impact of small molecule inhibitors that target the RAS/RAF/MEK/ERK signaling pathway on autophagy is discussed in this study. The advantages and limitations of the clinical combination of these small molecule inhibitors with autophagy inhibitors are also explored. The findings from this study may provide additional perspectives for future cancer treatment strategies.
RAS/RAF/MEK/ERK 信号通路是丝裂原活化蛋白激酶(MAPK)最重要的通路之一,广泛参与调节细胞增殖、分化、凋亡和信号转导。自噬是一种通过降解衰老和受损细胞器来维持细胞内稳态的基本机制。最近的一些研究表明,RAS/RAF/MEK/ERK 信号通路与自噬调节密切相关,在肿瘤细胞中具有双重作用。然而,RAS/RAF/MEK/ERK 信号通路参与自噬调节的具体机制尚不完全清楚。本文全面综述了 RAS/RAF/MEK/ERK 信号通路与自噬及其在癌症治疗中的相互作用的研究进展。本文还讨论了针对 RAS/RAF/MEK/ERK 信号通路的小分子抑制剂对自噬的影响。探讨了这些小分子抑制剂与自噬抑制剂联合应用于临床的优缺点。本研究的结果可能为未来的癌症治疗策略提供额外的视角。