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Emerging Applications of the Tumor Necrosis Factor Family of Ligands and Receptors in Cancer Therapy

Anas Younes, Marshall E. Kadin

From the Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA.

Address reprint requests to Anas Younes, MD, Department of Lymphoma and Myeloma, Unit 429, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: ayounes{at}mail.mdanderson.org.

Abnormalities of the tumor necrosis factor (TNF) family members have been linked to several human diseases, including cancer. Novel treatment strategies for cancer are emerging based on an understanding of the function of TNF family members. The advantage of these strategies is their potential to selectively target cancer cells, while sparing normal cells. Combining these new strategies with currently available treatments such as chemotherapy and radiation therapy is under investigation, with promising results. However, because some TNF family members are toxic to normal mammalian cells when administered systemically, only a few TNF family members have potential therapeutic value. This concise review focuses on the clinical implications of four TNF family members for cancer treatment: CD30/CD30 ligand, CD40/CD40 ligand, receptor activator of nuclear factor-B (RANK)/RANK ligand, and TNF-related apoptosis-inducing ligand (TRAIL) Apo-2L/TRAIL receptors.

Supported by NIH grants P30 CA 26672 (AY) and P0 CA 93683 (MEK).

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