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Figure 2. Targeting cancer-associated fibroblasts (CAFs) in cancer. Four main strategies targeting cancer-associated fibroblasts (CAFs) as cancer treatment are discussed. CAFs can be depleted by several treatments targeting CAF-specific markers, such as FAP and α-SMA. The normalization of CAFs from a pro-tumorigenic status to a quiescent or tumor-suppressive state can also be used for cancer treatment with small molecules such as ATRA or VDR ligands. The crucial signalings for CAF tumor-promoting function, such as cytokines and growth factors signalings, can be targeted to inactivate CAFs. Finally, CAF-derived extracellular matrix (ECM) proteins or related signalings can be targeted to induce ECM remodeling. MDSC: Myeloid-derived suppressor cell; FAP: fibroblast activation protein; CAR: chimeric antigen receptor; ATRA: all-trans retinoic acid; VDR: vitamin D receptor; FGFR: fibroblast growth factor receptor; SMO: smoothened; MMP: matrix metalloproteinase.