Recent Advances in TGF-β Inhibitors for the Therapeutic Management of Cancer and Fibrosis
A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".
Deadline for manuscript submissions: 30 November 2024 | Viewed by 27497
Special Issue Editor
Interests: Function and regulation of TGF-beta expression and signaling in prostate and renal cancers; androgen receptor signaling; cross-talk of TGF-beta with IGF-I, AKT, mTOR, androgen receptor, and Hic-5; survivin in cancer; Notch/Jagged1 signaling; drug discovery; YM155; mTOR inhibitors; TGF-beta signaling inhibitors; apoptosis; hypoxia and hypoxia-inducible pathways; AMPKs; chemoprevention; polyphenols
Special Issue Information
Dear Colleagues,
TGF-βs are highly conserved 25 kDa secretory proteins that signal through binding to and activating transmembrane serine-threonine kinase receptors. TGF-βs control many vital normal cellular and physiological processes such as apoptosis, growth control, differentiation, extracellular matrix production, epithelial-mesenchymal transition, angiogenesis, wound-healing, development and immune regulation. There are three TGF-β isoforms in mammals, namely TGF-β1, TGF-β2 and TGF-β3, each of which has a unique tissue expression profile, and their normal functions are both cell-type and context-dependent. Despite the well-documented tumor suppressor function of TGF-βs, TGF-β signaling has a dark side in cancer as it drives the growth, aggressiveness, and therapeutic resistance of many cancers. Another major dark side of TGF-β signaling is in driving fibrosis associated with many pathologies, and TGF-βs thus likely contribute to liver cirrhosis, chronic kidney disease, aortic stenosis, gastrointestinal strictures, cardiomyopathy, and pulmonary fibrosis. It is thus without surprise that major efforts have been taken to develop therapeutic inhibitors targeting TGF-βs and various components of TGF-β pathways. Although many TGF-β inhibitors have failed in clinical trials due to dose-limiting toxicities or inadequate responses, some of them are gaining enthusiastic support with potential to improving patient outcome, particularly in the setting of immune checkpoint inhibitors in cancer. This Special Issue is focused on summarizing the state-of-the-art findings, current research and future trends in the development and use of TGF-β pathway inhibitors for the therapeutic management of cancers and fibrosis.
Prof. Dr. David Danielpour
Guest Editor
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Keywords
- TGF-β
- metastasis
- EMT
- immunotherapy
- fibrosis
- Smad2
- Smad3
- angiogenesis
- ligand traps
- soluble receptors
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