Transforming growth factor beta 1 and 2 signaling pathway (TGF-β1/TGF-β2 pathway)

The Transforming growth factor beta 1 and 2 (TGF-β1/2) signaling pathway is a pleiotropic regulator of cell growth, differentiation, and immune homeostasis [1][11]. In healthy tissues, it functions as a tumor suppressor by inducing cell cycle arrest and apoptosis; however, in advanced disease states, it is often co-opted to drive progression [6][7]. In oncology, the pathway promotes the epithelial-mesenchymal transition (EMT), metastasis, and the creation of an immunosuppressive tumor microenvironment [4][12]. In fibrotic conditions, it is the primary driver of excessive extracellular matrix deposition and tissue scarring [2][8]. Therapeutic interventions include neutralizing antibodies, small molecule kinase inhibitors of the TGF-β type I receptor (ALK5), and antisense oligonucleotides [1][3]. Despite its potential, clinical development is complicated by safety concerns such as cardiotoxicity and the development of skin lesions [2][14].

Other names

TGF-beta 1/2 signaling pathwayTGFB1/TGFB2 signalingTransforming growth factor beta 1/2 pathwayTGF-beta signaling cascade

Drugs targeting the TGF-β1/2 pathway primarily act by neutralizing the ligands (antibodies), trapping the ligands (fusion proteins), inhibiting the serine/threonine kinase activity of the TGF-β type I receptor (ALK5), or suppressing ligand mRNA translation (antisense oligonucleotides) [1][3][8].