Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.

Cancer-associated stromal cells, particularly cancer-associated fibroblasts (CAFs), are pivotal components of the tumor microenvironment (TME) that significantly influence cancer progression. Communication between CAFs and cancer cells orchestrates key aspects of tumor dynamics, including the induction of dormancy. In response to adverse environmental stimuli, such as hypoxia, chemotherapy, or radiotherapy, cancer cells enter a dormant state, enabling them to evade environmental stimuli. The duration of this dormancy varies with the type, differentiation degree, and proliferation rate of primary cancer. The process is regulated by CAFs through various mediators, including growth factors, chemokines, inflammatory factors, exosomes, etc. Notably, environmental stimuli can induce the formation of polyploid giant cancer cells (PGCCs), a dormant cell type characterized by high drug resistance, tumorigenicity, and stemness. This review summarizes the relationship between CAFs and cancer cell dormancy, and explores the potential mechanisms through which CAFs regulate this process.