Reprogramming Cancer-associated Fibroblast: the Emerging Role of Traditional Chinese Medicine

Cancer-associated fibroblasts (CAFs) are one of the most abundant stromal components in tumor microenvironment (TME), which participate in key processes such as extracellular matrix remodeling, immune regulation, metabolic support and treatment tolerance. In recent years, with the development of single-cell sequencing and spatial omics technology, people's understanding of CAFs has gradually changed from unified cancer cell population to a dynamic cell collection with diverse sources, continuous states and heterogeneous functions. Numerous studies have shown that CAFs have a high degree of dynamic plasticity, and their phenotype can undergo reversible or semi-reversible transformation driven by different microenvironmental signals. The plasticity of CAFs not only explains the functional heterogeneity of CAFs across studies, but also provides a theoretical basis for changing the therapeutic strategy of targeting CAFs from removal to reprogramming. Among them, it is a significant advantage of traditional Chinese medicine (TCM) to reprogram CAFs through network regulation. This article systematically reviews the source and classification system of CAFs. In addition, aiming at the off-target and drug resistance problems in tumor treatment, this article focuses on the unique mechanism of traditional Chinese medicine monomers and compounds reprogramming CAF phenotype with the synergistic advantages of multi-component, multi-target and multi-pathway. This paper aims to provide a new theoretical basis and strategic direction for breaking through the bottleneck of tumor treatment.