Fibroblasts and extracellular matrix (ECM) (ECM)

Fibroblasts are the primary cells responsible for the synthesis and maintenance of the extracellular matrix (ECM), a complex network of proteins and carbohydrates that provides structural and biochemical support to surrounding cells (Source: NIH, PMC6163531). In healthy tissue, fibroblasts and the ECM are essential for wound healing and tissue integrity; however, their dysregulation is a hallmark of various pathologies, including organ fibrosis and cancer (Source: Nature Reviews Drug Discovery, 2017). In the tumor microenvironment, cancer-associated fibroblasts (CAFs) produce a dense ECM that can act as a physical barrier to drug delivery and promote tumor progression (Source: PubMed, 30272968). Therapeutic strategies targeting this system often focus on inhibiting fibroblast activation, blocking pro-fibrotic signaling pathways like TGF-beta, or enzymatically degrading excessive ECM components to improve tissue function or enhance the penetration of other therapies (Source: StatPearls, Idiopathic Pulmonary Fibrosis). Furthermore, the ECM serves as a reservoir for growth factors, and its remodeling by matrix metalloproteinases (MMPs) is a critical step in both physiological and pathological processes (Source: UniProt, Matrix Metalloproteinases). Targeting the fibroblast-ECM axis remains a significant challenge due to the risk of systemic toxicity and the necessity of maintaining normal tissue repair mechanisms (Source: PubMed, 29120461).

Other names

Connective tissueStromaTumor microenvironmentExtracellular matrix

Drugs targeting this system typically inhibit fibroblast activation and proliferation, enzymatically degrade specific ECM components like collagen or hyaluronan, or block pro-fibrotic signaling pathways such as TGF-beta.