Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy

Cancer-associated fibroblasts (CAFs) are an abundant and diverse cell population within tumor microenvironments of solid tumors. Multiple subtypes of CAFs, defined by molecular and functional markers, have been described in the literature. CAFs contribute to tumor progression by remodeling the extracellular matrix, promoting immune evasion, and supporting angiogenesis and metastasis. Fibroblast activation protein (FAP) is a transmembrane serine protease minimally expressed in normal adult tissues but significantly upregulated in certain subtypes of CAFs across many solid tumors. High levels of FAP have been associated with poor prognosis in various cancers. FAP has increasingly emerged as a promising target for both imaging and therapy. Multiple FAP-targeting strategies, such as small molecules, monoclonal antibodies, drug conjugates, and radiolabeled ligands, are currently being investigated in preclinical and early clinical settings. This review provides a clinically focused overview of CAFs in the tumor microenvironment, highlighting key fibroblast markers, their associations with prognosis across various tumor types, and their utility in radiologic imaging and targeted therapy. We also discuss the potential of non-FAP fibroblast targeting molecules and the clinical rationale for more selective, subtype-specific strategies. By examining fibroblast biology through a radiologist's lens, we aim to explore the evolving role of stromal targeting in imaging and the treatment of solid tumors.