Targeting the TME-Autophagy Axis to Overcome Cancer Drug Resistance
DOI:
https://doi.org/10.54097/wbp6y702Keywords:
Tumor microenvironment, cellular autophagy, metabolic reprogramming, drug resistance, Targeted therapy.Abstract
The tumor microenvironment (TME), as an essential ecological niche for tumor cell survival, is composed of stromal cells, immune cells, extracellular matrix, and signaling molecules. It not only provides metabolic support for tumors but also promotes their proliferation, invasion, and treatment resistance through dynamic regulation. Autophagy, a key mechanism in cellular homeostasis, plays a dual role in tumors: early on, it inhibits malignant transformation by clearing damaged organelles, while later it supports tumor survival through metabolic adaptation. Recent studies have revealed extensive interactions between TME and autophagy. For example, hypoxia and nutrient deprivation can activate autophagy pathways, while autophagy-derived metabolites can reshape the components of the TME. This mechanism plays a crucial role in tumorigenesis and its drug resistance characteristics. However, most current drugs (such as autophagy inhibitors or anti-angiogenesis drugs) target single pathways, failing to block the autophagy-TME interaction, which forms a resistance network. This review will analyze the mechanisms of the autophagy-TME interaction in the development of drug resistance during different stages of cancer and discuss strategies that may improve the therapeutic efficacy of cancer treatments.
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