Felipe Samaniego, M.D.

The Samaniego lab has identified potential inhibitors of death receptors and will target these inhibitors to facilitate tumor cell death.

Almost all of the 60,000 lymphoma cancers occurring annually in the United States have no known etiology, and nearly half of those diagnosed will die with the disease. Advances in treatment have been hampered by minimal knowledge of defective regulation of cancer cell death. Our research team in the Department of Lymphoma and Myeloma is studying how to efficiently kill lymphoma and blood cancer cells.

Cells normally undergo suicide after death receptors Fas and TRAIL are switched on. But in cancer cells, this switch is defective, and cells do not die. We discovered that the cancer-causing human herpes virus-8 K1 protein binds Fas and blocks the Fas death receptor and cells do not die. Likewise, we have also identified cellular death receptor inhibitors CD74 and p100, which are highly expressed in cancer cells and block cell death.

To improve cancer therapy by facilitating cancer death, we plan to show how these inhibitors block cancer cell death and investigate how to block these inhibitors. We will investigate how the inhibitors bind Fas and design short proteins that compete with binding in order to facilitate cell death. We will test the short proteins in mice to show whether they block the inhibitor, causing cell death.

These experiments will serve as the basis for developing anticancer drugs and testing them in clinical trials for patients who lack effective therapies. Support for our research is provided by grants from various agencies, fellowships and gifts from the many grateful patients treated at MD Anderson Cancer Center.