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  • Therapeutic Role of Transforming Growth Factor- β on Cancer

  • Mehrdad Ostadpoor,1,* Majid Gholami-Ahangaran,2
    1. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
    2. Associate Professor, Group of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran


  • Introduction: Transforming Growth Factor-β (TGFβ) is a vast superfamily of cytokines that includes TGF-βs (TGF-β1, -β2, and -β3), activins, inhibins, Anti-Mullerian Hormone (AMH), Bone Morphogenic Protein (BMPs), Growth Differentiation Factors (GDFs), Glial-derived Neurotrophic Factors (GDNFs), and nodal. Transforming growth factor β (TGFβ) plays a crucial role in various processes, such as cell migration and invasion, inhibition of epithelial, hematopoietic, and immune cell growth, epithelial-to-mesenchymal (EMT) transition, and extracellular matrix remodeling. TGF-β exerts its tumor suppressive role by regulating cell proliferation, apoptosis, and immune cell modulation. The absence of TGF-β1 results in severe inflammatory responses by activating the immune cell population and causing the infiltration of lymphocytes and macrophages in various organs. Additionally, its ability to arrest the cell cycle at the early G1 phase and inhibit the growth of various cell types is well documented.
  • Methods: In this study, keywords including Transforming Growth Factor-β, Cancer, and Treatment were reviewed from the Mesh list and other reputable websites such as PubMed, Science Direct, and Google Scholar, and the data was organized. The searches included all published papers from 2010 to 2023. Full text papers were considered, while those manifesting only as abstracts were excluded. Only full papers focusing on the specific role of transforming growth factor-β in cancer treatment were selected. A total of 50 papers were chosen and studied in this review.
  • Results: Evidence suggests that TGF-β promotes the activation of tumor suppressor genes such as p15, p21, and attenuates the tumor-promoting gene c-MYC expression, thereby supporting its antitumor effect. Articles also showed that TGF-β limits cancer formation by activating the apoptotic pathway. Downstream targets for the pro-apoptotic functions of TGF include death-associated protein kinase (DAPK), growth arrest, and DNA damage. Numerous preclinical results from in vitro cell models and in vivo animal models have demonstrated the great potential of anti-tumor therapeutics with TGFβ-neutralizing antibodies and ligand traps that block the interaction of TGFβ with its receptors or selective small-molecule TGFβ receptor kinase inhibitors. Several studies have shown that TGF-β acts as a tumor suppressor by inhibiting proliferation and inducing apoptosis during the early stages of tumorigenesis. Generally, TGF-β inhibits proliferation and promotes apoptosis by overexpressing cyclin-dependent kinase (CDK) inhibitors and downregulating MYC expression. TGF-β mainly regulates cell proliferation by inhibiting cell cycle progression through G1 arrest. In epithelial cells, it executes a coordinated cytostatic program with dual effects by inducing CDK inhibitors p21Cip1 and p15Ink4b to arrest cell proliferation, and suppressing proliferative drivers. Treatment of tumor cells with a combination of vaccines and antisense TGF-β therapy has shown a reduction in tumor size and increased survival benefit.
  • Conclusion: Anti-TGFβ therapeutic drugs, including TGFβ-neutralizing antibodies, peptide inhibitors, TGFβ receptor kinase inhibitors, antisense oligonucleotides, and TGFβ ligand traps, were developed for the treatment of cancer, fibrosis, and other diseases with aberrant vascular symptoms. TGF-β intervenes in critical processes linked to tumor development and progression, making this factor a promising molecular target in cancer treatment. The enormous variety of molecules involved in TGFβ synthesis, activation, or signal transduction, as well as those capable of indirectly affecting these mechanisms, represent potential therapeutic targets under research.
  • Keywords: Transforming Growth Factor- β, Cancer, Treatment

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