Exploring anti-TGF-β therapies in cancer and fibrosis
2011 (English)In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 29, no 4, 140-152 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2011. Vol. 29, no 4, 140-152 p.
Endocrinology and Diabetes Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-168730DOI: 10.3109/08977194.2011.595411ISI: 000292706200004PubMedID: 21718111OAI: oai:DiVA.org:uu-168730DiVA: diva2:503299