Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment

Pancreatic cancer (PC) is a highly aggressive cancer characterized by a unique tumor microenvironment (TME) that confers resistance to traditional therapies. As the dominant stromal cells in the TME, cancer-associated fibroblasts (CAFs) promote PC progression by modulating the extracellular matrix and interacting with surrounding cells. Numerous PC treatment strategies targeting CAFs have been explored in the past decade. However, targeting different subtypes of CAFs leads to varying therapeutic outcomes, highlighting the intricate and multifaceted nature of CAFs. The heterogeneity and dynamism of CAFs increase the complexity and challenges associated with tumor therapeutics. Currently, combination therapies incorporating CAF-targeted approaches in PC treatment have shown encouraging outcomes in select clinical trials. A comprehensive understanding of CAFs is essential for developing individualized therapeutic approaches. This review outlines the current knowledge of CAF heterogeneity, crosstalk with surrounding cells, and strategies for targeting CAFs in PC, aiming to keep researchers and clinicians up-to-date with the latest information on CAFs in PC.