Cancer associated fibroblast: Mediators of tumorigenesis

It is well accepted that the tumor microenvironment plays a pivotal role in cancer onset, development, and progression. The majority of clinical interventions are designed to target either cancer or stroma cells. These emphases have been directed by one of two prevailing theories in the field, the Somatic Mutation Theory and the Tissue Organization Field Theory, which represent two seemingly opposing concepts. This review proposes that the two theories are mutually inclusive and should be concurrently considered for cancer treatments. Specifically, this review discusses the dynamic and reciprocal processes between stromal cells and extracellular matrices, using pancreatic cancer as an example, to demonstrate the inclusivity of the theories. Furthermore, this review highlights the functions of cancer associated fibroblasts, which represent the major stromal cell type, as important mediators of the known cancer hallmarks that the two theories attempt to explain.