|
|
|
|
|
|
|
|
|
|
|||||||
 |
 |
 |
||||||||||||
|
Preclinical Studies Reveal Effectiveness of Therapies for Pediatric Cancers
Researchers in the Children’s Cancer Hospital at M. D. Anderson recently reported preclinical results for anti-cancer approaches in neuroblastoma and acute myelogenous leukemia, potentially paving the way for new clinical treatments. All of the agents tested in the studies, which were presented last month at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology (ASPHO), are either in trials for other cancers or may begin early clinical testing this year. “We hope that these agents will one day make it to our pediatric patients, who often run out of new treatment options,” said Patrick Zweidler-McKay, M.D., Ph.D., senior investigator on the studies and an assistant professor in pediatrics. Neuroblastoma In one study, a glycolysis inhibitor named 3-BrOP was shown to starve neuroblastoma cells by blocking the cells’ ability to derive energy from sugar. 3-BrOP reduced human tumor growth in mice by more than 75%. The researchers found that neuroblastoma cells are much more dependent on glycolysis for energy than normal cells, which explains why the 3-BrOP was effective. The agent, developed at M. D. Anderson, has previously been shown to have efficacy against glioblastoma, colon cancer, lymphoma, and acute leukemia. Another neuroblastoma study presented at ASPHO targeted the tumor by inhibiting its blood supply. In this study, investigators used the mobilizing agent AMD3100 and unexpectedly found that it disrupted tumor growth by reducing the number of tumor blood vessels. Daily treatment with AMD3100 reduced tumor growth in mice by more than 75%. In a third study focusing on neuroblastoma, researchers tested a novel multi-kinase inhibitor, vandetanib. “By itself, vandetanib inhibited neuroblastoma tumor growth in mice by two-thirds and decreased blood vessel formation around the tumors,” said Peter Zage, M.D., Ph.D., an assistant professor in pediatrics and the investigator who presented the findings. “When vandetanib was combined with 13-cisretinoic acid (CRA), the impact on tumor growth was even greater.” Mice treated with the combination of vandetanib and CRA, a drug used to treat severe acne, had an 86% reduction in tumor growth.
CRA was previously known to differentiate neuroblastoma cells into benign cells when used in combination therapies, though it has no direct action against the cancer. A first-in-children phase I clinical trial of the vandetanib-CRA combination is now open at M. D. Anderson for children whose neuroblastoma has relapsed. The findings of the neuroblastoma studies are important because current therapies have limited effectiveness. Neuroblastoma is the most common extra-cranial solid tumor in children, and nearly two-thirds of those children are diagnosed after the disease has metastasized. Leukemia In another study involving mice harboring human acute myelogenous leukemia cells, a novel tropomyosin receptor kinase inhibitor named AZ23 was shown to reduce the levels of circulating leukemia cells by more than half within 1 week. Meanwhile, in mice treated for 4 weeks, the leukemia was eradicated and remained undetectable in 60% of the mice for several months. Importantly, the researchers found that AZ23 was more effective against human acute myelogenous leukemia cells that express high levels tropomyosin receptor kinase A, a nerve growth factor receptor, which could guide treatment with the drug in the future. Pediatric acute myelogenous leukemia has a cure rate of only 50%, compared with the more common acute lymphoblastic leukemia, which is cured in 80% of pediatric patients. As with neuroblastoma, new treatments for acute myelogenous leukemia are badly needed, and thus investigators are encouraged by the preclinical results seen with AZ23. “Now that we have found a new, targetable growth pathway in acute myelogenous leukemia, we may be able to use AZ23 to treat both children and adults with the disease,” said Dr. Zweidler-McKay.For more information, call Dr. Zage at 713-792-6624 or Dr. Zweidler-McKay at 713-563-5394. Other articles in OncoLog, May 2009 issue:
Home/Current Issue | Previous Issues | Articles by Topic | Patient Education ©2009 The University of Texas M. D. Anderson Cancer Center |
|||||||||||
TOP