Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets

作者：Jiamin Zhu, Liting Lv, Yuqian Yan, Simin Wang, X Y Lu, Xiaoting Ma, Xia Sun, Ya Qin, Hsin-Mao Wu, Guiping yu, Q. Jane Wang, Xiao Liang · 发表于：Molecular Biomedicine · 年份：2026 · DOI：10.1186/s43556-026-00430-7 · 被引用次数：6 · 研究领域：Autophagy in Disease and Therapy、Cancer, Hypoxia, and Metabolism、Endoplasmic Reticulum Stress and Disease

Autophagy represents a conserved lysosome-dependent catabolic mechanism that safeguards cellular energetic homeostasis and supports adaptive metabolic remodeling under diverse stress conditions. In cancer, autophagy displays a highly context-dependent "double-edged sword" behavior. During the early stages of tumorigenesis, autophagy can suppress malignant transformation by preserving genomic stability, restraining chronic inflammation, and limiting the acquisition of malignant stemness, thereby helping preserve cellular integrity in early tumorigenesis. However, as tumors progress, autophagy can be reprogrammed into an adaptive survival mechanism that supplies tumor growth, metastatic dissemination, and resistance to multiple therapeutic modalities in response to hypoxia, nutrient deprivation, and therapeutic stress. Within the framework of tumor evolution, this review systematically integrates the molecular mechanisms and regulatory networks underlying different forms of autophagy, including canonical, non-canonical, and selective forms. We explore how autophagy intersects with metabolic reprogramming, immune signaling, DNA damage responses, and regulated cell death, and discuss its involvement in tumor progression, microenvironment remodeling, metastasis, and therapy resistance, with relevance to interactions between tumor cells and the surrounding microenvironment. We also summarize recent developments in autophagy-targeted approaches, including chloroquine derivatives, em...