DIVERSITY AND BIOLOGY OF CANCER-ASSOCIATED FIBROBLASTS

Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite the presence of non-neoplastic stromal components that substantially contribute to the progression of the tumor. Indeed, cancer cell survival, growth, migration, and even dormancy are influenced by the surrounding tumor microenvironment (TME). Within the TME, cancer-associated fibroblasts (CAFs) have been shown to play several roles in the development of a tumor. They secrete growth factors, inflammatory ligands, and extracellular matrix proteins that promote cancer cell proliferation, therapy resistance, and immune exclusion. However, recent work indicates that CAFs may also restrain tumor progression in some circumstances. In this review, we summarize the body of work on CAFs, with a particular focus on the most recent discoveries about fibroblast heterogeneity, plasticity, and functions. We also highlight the commonalities of fibroblasts present across different cancer types, and in normal and inflammatory states. Finally, we present the latest advances regarding therapeutic strategies targeting CAFs that are undergoing preclinical and clinical evaluation.

Automated summary

Efforts to develop anti-cancer therapies have mainly targeted the epithelial compartment, but recent studies have shown the significant influence of cancer-associated fibroblasts (CAFs) in tumor progression. CAFs not only promote cancer cell proliferation, therapy resistance, and immune exclusion, but may also restrain tumor progression in certain contexts. Research on CAFs has focused on their heterogeneity, plasticity, and functions across different cancer types and states, as well as advancements in therapeutic strategies targeting CAFs currently undergoing preclinical and clinical evaluation.