Cancer-Associated Fibroblast Functions as a Road-Block in Cancer Therapy

SIMPLE SUMMARY: An overwhelming percentage of deaths in solid tumors are caused by treatment failure due to the disease’s unresponsiveness when tumor cells tolerate treatment. Aggressive cancer contains tumors cells that are surrounded by many other non-tumor cells, including fibroblasts cells. These fibroblasts near tumor cells are converted by the tumor cells into specialized fibroblasts called cancer-associated fibroblasts that favor the growth of tumors. This review examines how cancer-associated fibroblasts interact with tumor cells, immune cells, and endothelial cells in aiding and abetting the development of resistance to different types of cancer therapy. As cancer-associated fibroblasts’ function blocks the road to recovery, we need to neutralize their function for the clinical management of the disease to be successful. The knowledge about the role of cancer-associated fibroblasts in resisting therapy is fundamental to design an appropriate remedy to counteract drug resistance and improve the outcome of the disease. ABSTRACT: The journey of a normal resident fibroblast belonging to the tumor microenvironment (TME) from being a tumor pacifier to a tumor patron is fascinating. We introduce cancer-associated fibroblast (CAF) as a crucial component of the TME. Activated-CAF partners with tumor cells and all components of TME in an established solid tumor. We briefly overview the origin, activation, markers, and overall functions of CAF with a particular reference to how different functions of CAF in an established tumor are functionally connected to the development of resistance to cancer therapy in solid tumors. We interrogate the role of CAF in mediating resistance to different modes of therapies. Functional diversity of CAF in orchestrating treatment resistance in solid tumors portrays CAF as a common orchestrator of treatment resistance; a roadblock in cancer therapy