Research presented at the annual meeting of the American Association for Cancer Research provided new insights into the role and function of a natural molecule called TRAIL that is part of the death-inducing machinery necessary to stop cancer.
TRAIL - which stands for tumor necrosis factor (TNF)-related apoptosis-inducing ligand - is a recently identified member of the TNF superfamily. When TRAIL binds to death receptors, rapid cell death follows in various human cancer cell lines. TRAIL suppresses the growth of TRAIL-sensitive human cancers (including breast, colon, prostate, pancreas, glioblastoma, ovarian, and cervical cancers) implanted in mice; and in combination with some conventional chemotherapies, it suppresses tumor growth that otherwise resists treatment with TRAIL or chemotherapy alone.
A study examining the TRAIL-related, novel monoclonal antibody TRA-8 combined with doxorubicin hydrochloride (AdriamycinŽ) or paclitaxel (TaxolŽ) on tumor-growth inhibition in a mouse model of human breast cancer found that together, the two agents achieved a higher percentage of complete regressions than either one alone.
"Complete regression occurred in 71% of animals receiving TRA-8 plus Adriamycin, and 38% of animals receiving TRA-8 and paclitaxel," said Donald J. Buchsbaum, Ph.D., professor and director, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama-Birmingham. "The response was less in animals treated with TRA-8 alone, and regression did not occur with chemotherapy alone."
TRAIL binds to two death receptors (DR4 and DR5) and two decoy receptors (DcR1 and DcR2) in the cell. TRA-8 selectively targets only one death receptor, DR5, which is primarily expressed by cancer cells but not normal cells. This selectivity may give the TRA-8 monoclonal antibody advantages over TRAIL, according to the Alabama research team.
The group plans further research with other breast tumor models, and will investigate combination treatment with radiation therapy. They will also investigate the mechanism that makes combined treatment more effective. Studies are planned in several models of ovarian, colon, prostate, and pancreatic cancer.
SOURCES:
93rd Annual Meeting of the American Association for Cancer Research, April 9, 2002, San Francisco, CA
University of Alabama-Birmingham Comprehensive Cancer Center (http://www.ccc.uab.edu)
