CAF-mediated tumor vascularization: From mechanistic insights to targeted therapies.

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment (TME) and play a crucial role in tumor progression. The biological properties of tumors, such as drug resistance, vascularization, immunosuppression, and metastasis are closely associated with CAFs. During tumor development, CAFs contribute to tumor progression by remodeling the extracellular matrix (ECM), inhibiting immune cell function, promoting angiogenesis, and facilitating tumor cell growth, invasion, and metastasis. Studies have shown that CAFs can promote endothelial cell proliferation by directly secreting cytokines such as vascular endothelial growth factor (VEGF) and fibroblast Growth Factor (FGF), as well as through exosomes. CAFs also secrete the chemokine stromal cell-derived factor 1 (SDF-1) to recruit endothelial progenitor cells (EPCs) into the peripheral blood and guide their migration to the tumor periphery. Additionally, CAFs can induce tumor cells to transform into "endothelial cells" that participate in vascular wall formation. However, the precise mechanisms remain to be further investigated. Due to their widespread presence in various solid tumors and their tumor-promoting function, CAFs are emerging as therapeutic targets. In this review, we summarize the specific mechanisms through which CAFs promote angiogenesis and outline current therapeutic strategies targeting CAF-induced vascularization, ongoing clinical trials targeting CAFs, and discuss potential future treatment approaches. We hope this will contribute to the advancement of CAF-targeted tumor treatment strategies.