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Role of Transforming Growth Factor Beta in Human Cancer

From the Duke University Medical Center, Departments of Medicine and Pharmacology and Cancer Biology, Durham, NC

Address reprint requests to e-mail: Gerard C. Blobe, MD, PhD, Departments of Medicine and Pharmacology and Cancer Biology, Duke University Medical Center, 221 BMSRB Research Drive, Box 2631 DUMC, Durham, NC 27710; e-mail: blobe001{at}mc.duke.edu

Transforming growth factor beta (TGF-ß) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. Alterations in the TGF-ß signaling pathway, including mutation or deletion of members of the signaling pathway and resistance to TGF-ß-mediated inhibition of proliferation are frequently observed in human cancers. Although these alterations define a tumor suppressor role for the TGF-ß pathway in human cancer, TGF-ß also mediates tumor-promoting effects, either through differential effects on tumor and stromal cells or through a fundamental alteration in the TGF-ß responsiveness of the tumor cells themselves. TGF-ß and members of the TGF-ß signaling pathway are being evaluated as prognostic or predictive markers for cancer patients. Ongoing advances in understanding the TGF-ß signaling pathway will enable targeting of this pathway for the chemoprevention and treatment of human cancers.

Supported by the National Institutes of Health/National Cancer Institute (grant Nos. CA91816, CA100065 and CA105255), the American Heart Association, the American Cancer Society, the Elsa U. Pardee Foundation, and a V Scholar Award from The V Foundation for Cancer Research (to G.C.B.). R.L.E. is supported by the Medical Scientist Training Program.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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