Cancer cells and cancer-associated fibroblasts

Cancer cells and cancer-associated fibroblasts (CAFs) constitute a primary axis of the tumor microenvironment (TME), where their bidirectional communication drives malignancy (PubMed: 31091486). CAFs are a heterogeneous population of activated fibroblasts characterized by the expression of markers such as Fibroblast Activation Protein (FAP) and alpha-smooth muscle actin (α-SMA), which contribute to extracellular matrix remodeling and the secretion of pro-tumorigenic factors like TGF-β and IL-6 (PubMed: 28935672). This interaction promotes cancer cell proliferation, epithelial-mesenchymal transition (EMT), and metabolic reprogramming, while also creating a physical and chemical barrier against immune cell infiltration and chemotherapy (NIH: PMC7279151). Therapeutic interventions targeting this relationship include FAP-directed antibodies, CAR-T cells, and inhibitors of stroma-derived signaling pathways to sensitize cancer cells to treatment (PubMed: 32603454). However, the functional diversity of CAFs poses a significant challenge, as some subsets may possess tumor-suppressive properties, making non-selective depletion potentially hazardous (PubMed: 30910717).

Other names

Tumor-stroma interactionCancer-CAF axisTumor microenvironmentMalignant cell-fibroblast crosstalk

Disruption of the tumor-supportive stroma, inhibition of paracrine signaling between fibroblasts and malignant cells, and depletion of activated fibroblast populations to enhance immune infiltration and drug delivery.