Cancer-Associated Fibroblasts: Challenges and Directions

Dear Colleagues,

Cancer-associated fibroblasts (CAFs) represent a significant cellular component within the tumor microenvironment (TME) and play a crucial role in facilitating tumor growth. They directly contribute to tumor progression by releasing various growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and various chemokines that stimulate angiogenesis and promote tumor development. Additionally, CAFs indirectly support tumor growth by secreting immune-suppressive cytokines like TGF-β, IL-8, and IL-10, and by remodeling the extracellular matrix (ECM), thereby rendering tumors resistant to various therapeutic interventions.

Cancer-associated fibroblasts (CAFs) are identified through several biomarkers, including α-SMA, PDGFRα/β, and fibroblast activation protein alpha (FAPα), among others. Notably, recent interest has grown around the reprogramming of the tumor microenvironment through the use of FAP-targeting ligand conjugates. This approach has gained prominence due to the exclusive overexpression of FAP in CAFs, with minimal to undetectable expression in healthy tissues. Currently, there are ongoing developments in the clinical use of ⁶⁸Ga/¹⁷⁷Lu-labeled FAP-targeting small molecules and peptide-based PET imaging agents, as well as radiotherapeutic agents.

This Special Issue will focus on original preclinical studies or comprehensive review articles. Topics can include the methods used to target CAF directly or indirectly until depletion of CAFs or elimination of tumor promotion, as well as the immunosuppressive function of CAFs using a combination of different therapeutic strategies for cancer treatment.

Dr. Paul J. Higgins
Dr. Ramesh Mukkamala
Guest Editors

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• cancer-associated fibroblast (CAFs)
• tumor microenvironment (TME)
• fibroblast activation protein alpha (FAPα)
• immunotherapy
• cytokines
• angiogenesis
• metastasis
• FAP inhibitors
• radioligands
• imaging agents