Targeting Cancer-associated Fibroblasts (CAFs) to Optimize Radiation Responses

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment with diverse functions. CAFs are heterogeneous; although their roles are primarily tumor-promoting, recent research suggests that in specific contexts, certain CAF subtypes may have tumour-restraining functions. Importantly, CAFs are capable of surviving following high doses of radiation. Here, CAFs typically undergo senescent changes, which trigger a diverse secretory phenotype. This phenotype presents a number of therapeutic opportunities for targeting CAFs to improve tumor cure rates following radiation. This review summarizes our current understanding of CAF development and heterogeneity, as well as presenting mechanisms by which CAFs are activated by radiation. Finally, recent examples demonstrate how targeting CAFs can synergize with radiation for therapeutic gain.