Stromal tissue remodeling (STR)

Stromal tissue remodeling is a complex biological process involving the physical and chemical reorganization of the extracellular matrix (ECM) and the activation of stromal cells, such as fibroblasts and myofibroblasts (Source: PMC6085356). In healthy conditions, it is critical for wound healing and development; however, in diseases like cancer and fibrosis, aberrant remodeling leads to increased tissue stiffness and the formation of a physical barrier that prevents drug delivery and immune cell infiltration (Source: Nature Reviews Cancer, 2016). Pathological remodeling is frequently driven by signaling pathways such as TGF-beta and Hedgehog, which trigger cancer-associated fibroblasts to overproduce collagen and hyaluronan (Source: PMC4943265). Therapeutic interventions aim to normalize this microenvironment through enzymatic degradation of ECM components or inhibition of pro-fibrotic signaling, thereby sensitizing tumors to conventional therapies (Source: PMC6085356). Despite its therapeutic potential, targeting stromal remodeling carries significant challenges, including the risk of facilitating metastasis by removing physical barriers and the potential for systemic toxicities like musculoskeletal syndrome (Source: PMC6085356).

Other names

Extracellular matrix remodelingECM remodelingTumor stroma modulationReactive stromaStroma-tumor crosstalk

Modulation of the extracellular matrix through enzymatic degradation of structural components (e.g., hyaluronan) or the inhibition of signaling pathways (e.g., Hedgehog, TGF-beta) and enzymes (e.g., LOXL2) that drive fibroblast activation and excessive matrix deposition.