Target intelligence / Profile preview

Transforming growth factor beta isoforms 1, 2, 3 (TGF-β1, 2, 3)

Target
TGF-β1, 2, 3
Molecular classification
Cytokine, Growth factor, Receptor ligand
01

Overview

Transforming growth factor beta (TGF-β) isoforms 1, 2, and 3 are pleiotropic cytokines that regulate a wide array of biological processes, including cell proliferation, differentiation, and immune homeostasis (Wikipedia, 2024). They signal through a heterotetrameric complex of type I and type II serine/threonine kinase receptors, which in turn activate the canonical SMAD pathway to modulate gene expression (NIH, 2014). In the context of oncology, these isoforms exhibit a paradoxical role, acting as tumor suppressors in early stages but promoting metastasis, angiogenesis, and immune evasion in advanced disease (NIH, 2013). Furthermore, TGF-β is a primary driver of pathological fibrosis across multiple organs, including the lungs, liver, and heart, by stimulating excessive extracellular matrix production (Frontiers, 2020). Therapeutic targeting of these isoforms involves monoclonal antibodies, ligand traps, and antisense technologies, though clinical progress has been tempered by safety concerns such as cardiotoxicity and the development of skin lesions (Frontiers, 2020; NIH, 2020).

Other names
TGF-betaTGFBTransforming growth factor beta 1, 2, and 3TGF-beta 1/2/3
02

Mechanism of action

Ligand neutralization via monoclonal antibodies or decoy receptors (traps), inhibition of ligand expression via antisense oligonucleotides or vaccines.

03

Biological functions

Signal transductionCell cycleApoptosisImmune responseCell proliferationCell differentiationWound healingEpithelial-mesenchymal transition
04

Disease associations

CancerInflammationFibrosisCardiovascular diseaseConnective tissue disease
05

Safety considerations

Cardiotoxicity (valvular hyperplasia)Cutaneous squamous cell carcinomasKeratoacanthomasBleeding eventsParadoxical tumor promotion in early-stage disease
06

Interacting drugs

Fresolimumab

10 more in the full profile.

07

Biomarkers

Plasma TGF-beta 1 levelsPhospho-SMAD2/3SMAD4 expressionTGF-beta responsive gene signature

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