In mouse models, Oxi4503 killed leukemia cells in addition to destroying the blood vessels that fed and nurtured them.
"It is very exciting to find one drug that can target both the leukemic cell and the endothelium to diminish the progression of leukemias those people who fail chemotherapy, early or late, could be treated with this drug to see whether they respond," said Shahin Rafii, M.D., a Howard Hughes Medical Institute Investigator and director of the Ansary Stem Cell Institute at Weill Cornell Medical College, who showed that leukemia cells are dependent on activated bone marrow blood vessels for survival and proliferation. Rafii is not affiliated with the UF study.
After Oxi4503 treatment, however, the researchers found that a thin layer of viable tumor tissue remained that was fed by newly formed vessels. The cells supplied by those vessels showed increased expression of a growth factor, as is often found in oxygen-deficient areas.
To disrupt this secondary formation of blood vessels, the researchers blocked the growth factor VEGF by administering an antibody called bevacizumab after the blood vessel-destroying agent OXi4503. The combined approach led to enhanced leukemia regression.
The research, funded by the National Institutes of Health and the Leukemia and Lymphoma Society, has implications for both basic science and clinical research, as the results suggest that potential therapies must be screened against not only leukemia cells, but also the environment with which they interact.
"It's a major paradigm shift," Rafii said.
Describing the studies as "elegant," Judith Karp, M.D., a professor of oncology and medicine and director of the leukemia program of the Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, said the findings support the notion that VEGF and the vascular milieu are extremely im
|Contact: Czerne M. Reid|
University of Florida