title: Exploring anti-TGF-β therapies in cancer and fibrosis.
abstract: Transforming growth factor-β (TGF-β) is a multifunctional cytokine, with important roles in maintaining tissue homeostasis. TGF-β signals via transmembrane serine/threonine kinase receptors and intracellular Smad transcriptional regulators. Perturbed TGF-β signaling has been implicated in a large variety of pathological conditions. Increased TGF-β levels have been found in patients with cancer, fibrosis, and systemic sclerosis, and were correlated with disease severity. In cancer, TGF-β mediates tumor invasion and metastasis by affecting both tumor cells and the tumor microenvironment including fibroblast activation and immune suppression. Furthermore, TGF-β is a strong stimulator of extracellular matrix deposition. On the basis of these observations, small molecule inhibitors of the TGF-β receptor kinases, neutralizing antibodies that interfere with ligand?receptor interactions, antisense oligonucleotides reducing TGF-β expression, and soluble receptor ectodomains that sequester TGF-β have been developed to intervene with excessive TGF-β signaling activity in the aforementioned disorders. Here, we review the current state of anti-TGF-β therapy in clinical trials.
authors: Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Lukas J A C
authors: LJ
authors: Hawinkels
authors: Peter
authors: P
authors: Ten Dijke
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D016376:Oligonucleotides, Antisense; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases