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Paracrine signaling pathways involving secreted factors like Vascular Endothelial Growth Factor (VEGF), Hepatocyte Growth Factor (HGF), and Transforming Growth Factor-beta (TGF-β) are critical for intercellular communication within the tissue microenvironment (PMID: 12459731). VEGF is the primary mediator of angiogenesis, promoting the formation of new blood vessels which is essential for tumor growth and wound healing (PMID: 15334063). HGF, through its receptor MET, regulates cell scattering, invasion, and protection from apoptosis, making it a key driver of cancer metastasis (UniProt: P14210). TGF-β is a pleiotropic cytokine that regulates immune responses and induces epithelial-mesenchymal transition, often facilitating immune evasion in advanced cancers (PMID: 27693023). These pathways are frequently dysregulated in diseases such as cancer and chronic fibrosis, where they promote pathological tissue remodeling. Therapeutic strategies include monoclonal antibodies like bevacizumab to neutralize VEGF or small molecule inhibitors like capmatinib to block HGF/MET signaling. Because this entry encompasses multiple distinct signaling molecules and their respective receptors, it represents a complex biological process rather than a single druggable target. Targeting these paracrine loops aims to disrupt the symbiotic relationship between diseased cells and their surrounding stroma.
Neutralization of secreted ligands or inhibition of their respective cognate receptor tyrosine kinases to block downstream signaling cascades.
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