MEMPHIS, Tenn., April 17 /PRNewswire/ -- Investigators at St. Jude Children’s Research Hospital have developed a strategy to speed future development of more effective and less toxic treatments for medulloblastoma, a type of brain cancer. Medulloblastomas arise in the back of the brain and account for about 20 percent of childhood brain tumors.
The new technique could also be used to identify specific pathways in other types of cancer that might be vulnerable to novel therapies. This could speed development of so-called molecular-targeted therapies for a wide variety of cancers. Molecular-targeted therapies work by blocking individual molecules that are crucial triggers of disease.
The key to the new St. Jude strategy is the ability to figure out in individual children which biochemical signaling pathway triggers and sustains the cancer. This is done by identifying key genes that are linked to that pathway. Like a light bulb that shows whether an electrical circuit is on, these genes are triggered when a specific biochemical pathway is abnormally activated in a tumor.
The investigators proved that this strategy is valid by demonstrating that it is possible to assign children with medulloblastoma into specific groups, depending on which biochemical signaling pathway is abnormally active. Based on this classification, novel drugs designed to block a key protein in each specific pathway could be correctly administered to the children most likely to respond to them.
“Our strategy lets us quickly determine which signaling pathway is abnormally activated by identifying in tumor samples the tell-tale genes that indicate which genes are mutated,” according to Richard Gilbertson, M.D., Ph.D., an associate member of the Department of Developmental Neurobiology at St. Jude and director of the Molecular Clinical Trials Core.
The technique could also be used to identify specific pathways in other types of cancer that might be vulnerable to novel therapies, and therefore speed development of so-called molecular targeted therapies for a wide variety of cancers. Molecular-targeted therapies work by blocking individual molecules that are key triggers of disease.
This new approach would avoid trial-and-error therapy that fails in patients who are not ideal candidates for a specific treatment. It would also reduce the chance that otherwise effective drugs would be abandoned because they failed in such patients during clinical trials. Gilbertson, the co- director of the St. Jude Neurobiology & Brain Tumor Program, is senior author of a paper on this work that appears in the April 20 issue of Journal of Clinical Oncology, which now appears in the online edition of that publication.
“Our work showed that drugs that target specific pathways are likely to be effective in distinct populations of patients with medulloblastomas,” said Margaret Thompson, M.D., Ph.D., clinical fellow in the Gilbertson lab. She is the first author of the paper. “We believe our technique will provide a rapid and accurate way to select appropriate patients for clinical trials of each molecular targeted therapy for medulloblastoma.”
Other authors of the study include Christine Fuller, Twala Hogg, James Dalton, David Finkelstein, Tom Curran and Amar Gajjar (St. Jude); Ching Lau, Murali Chintagumpala and Adekunle Adesina (Texas Children’s Hospital); David Ashley (Melbourne, Australia); Stewart Kellie (Sydney, Australia); and Michael Taylor (Hospital for Sick Children, Toronto).
This work was supported in part by the National Cancer Institute, the Sontag Foundation, the V-Foundation for Cancer Research, a Cancer Center (CORE) Support Grant and ALSAC.
St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org .
St. Jude Children’s Research Hospital
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