The Role of Cancer-Associated Fibroblasts in Tumor Progression

SIMPLE SUMMARY: As our knowledge of cancer as a complex organ comprising tumor cells as well as surrounding cells within the microenvironment continues to grow, it is imperative to consider how the microenvironment may be supporting the cancer and promoting tumor progression. One aspect of the microenvironment that has gained significant interest over the past decade are cancer-associated fibroblasts, which have been implicated in diverse oncogenic roles including cancer invasion and metastasis, resistance to existing cancer therapeutics, angiogenesis, and tumor proliferation. The identification of cancer-associated fibroblasts and the pathways through which they promote tumor progression will allow us to target a specific subset of cells within the cancer niche in order to augment existing cancer therapies and possibly develop novel methods. In this review, we discuss the different markers that have been used to identify cancer-associated fibroblasts in various cancer contexts as potential therapeutic targets and discuss the role that cancer-associated fibroblasts play in enhancing cancer malignancy. ABSTRACT: In the era of genomic medicine, cancer treatment has become more personalized as novel therapeutic targets and pathways are identified. Research over the past decade has shown the increasing importance of how the tumor microenvironment (TME) and the extracellular matrix (ECM), which is a major structural component of the TME, regulate oncogenic functions including tumor progression, metastasis, angiogenesis, therapy resistance, and immune cell modulation, amongst others. Within the TME, cancer-associated fibroblasts (CAFs) have been identified in several systemic cancers as critical regulators of the malignant cancer phenotype. This review of the literature comprehensively profiles the roles of CAFs implicated in gastrointestinal, endocrine, head and neck, skin, genitourinary, lung, and breast cancers. The ubiquitous presence of CAFs highlights their significance as modulators of cancer progression and has led to the subsequent characterization of potential therapeutic targets, which may help advance the cancer treatment paradigm to determine the next generation of cancer therapy. The aim of this review is to provide a detailed overview of the key roles that CAFs play in the scope of systemic disease, the mechanisms by which they enhance protumoral effects, and the primary CAF-related markers that may offer potential targets for novel therapeutics.