Drug Inhibits Neuroblastoma Blood Supply in Pre-Clinical Tests
Reduces tumor growth by 75 percent by disrupting blood vessel formationM. D. Anderson News Release 04/24/09
Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have found a way to prevent blood vessels from aiding the growth of neuroblastoma, a childhood cancer. The pre-clinical study was presented today in a platform session at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology.
Investigators at the Children's Cancer Hospital at M. D. Anderson have discovered that the drug, AMD3100, hinders the formation of tumor blood vessels and reduces human neuroblastoma tumor growth by more than 75 percent in mice.
The drug blocks interaction between SDF-1a and its receptor CXCR4. This pathway plays an important role in signaling cells to different areas of the body. More specifically, the study suggests that SDF-1a plays a role in differentiating and/or attracting pericyte-like cells to neuroblastoma tumors.
Pericytes are essential for organizing blood vessels to feed tumors. Without pericytes, blood vessels are dysfunctional and tumors are left without a vital blood source. This study found that AMD3100 decreased the number of pericyte-like cells in neuroblastoma tumors by close to 90 percent.
"AMD3100 works by shutting down the process that tumors need to set up vascular systems," says Patrick Zweidler-McKay, M.D., Ph.D., assistant professor at the Children's Cancer Hospital and senior investigator on the study. "The drug doesn't kill neuroblastoma cells directly, but it prevents tumors from growing rapidly by disrupting their blood supply."
In tissue culture, investigators were also able to show how AMD3100 prevented neuroblastoma cells from migrating toward SDF-1a ligands. SDF-1a is present at high levels in the bone marrow, one of two areas where neuroblastoma most commonly metastasizes.
"There is the possibility that this therapy could help prevent neuroblastoma metastasis to the bone marrow. However, more studies are needed to investigate this theory," says Zweidler-McKay.
According to the American Cancer Society, approximately 650 children, mainly under the age of five, are diagnosed with neuroblastoma in the United States each year. Close to two-thirds of these children are diagnosed after the cancer has metastasized to other parts of the body. For these patients with high-risk neuroblastoma, long-term survival is less than 40 percent because the tumors are often resistant to traditional chemotherapy.
Other investigators on the study were Alejandro Levy, M.D., Lindsey Nunnally, Lizhi Zeng, M.D., Wendy Fang, M.D., Keri Schadler, Riitta Nolo, Ph.D., and Peter Zage, M.D., Ph.D. 04/24/09