Transforming growth factor-beta: a target for cancer therapy.
Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor that regulates cell growth and differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis, and cellular immune responses. TGF-beta demonstrates paradoxical action whereby it can function to suppress early tumorigenesis; however, it can also facilitate malignant transformation and stimulate tumor growth by manipulating a more hospitable environment for tumor invasion and the development of metastases. Given the integral role of TGF-beta in transformation and cancer progression, various components of the TGF-beta signaling pathway offer potentially attractive therapeutic targets for cancer treatment. This review focuses on the role of TGF-beta in cancer and discusses both small and large molecule drugs currently in development that target TGF-beta, its receptor and important down stream steps along its signaling pathway.
Kelly
Ronan J
RJ
Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Morris
John C
JC
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000627:therapeutic use; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta