Researchers identify promising gene target for neuroblastoma therapyOctober 16, 2008BOSTON--Researchers at Dana-Farber Cancer Institute have identified a set of previously unknown mutations in a single gene in 8 percent of neuroblastomas, tumors of the nervous system that occur in young children and account for approximately 15 percent of all childhood cancer deaths. The discovery is intriguing because a small "targeted" molecule inhibitor caused neuroblastoma cell lines carrying two of the mutations to die when treated in the laboratory. This suggests that when mutations activate the gene, known as ALK, tumors become "addicted" to -- or dependent on -- the mutated gene for their continued growth. Therapies designed to inhibit ALK may offer an effective approach to the disease. For the research team and Dana-Farber itself, the finding is especially rewarding because funding for the study was provided in part by the Friends for Life Foundation, founded by the parents of a young Dana-Farber patient to support neuroblastoma research. The study appears in the Oct. 16 issue of the journal Nature. The lead author is Rani George, MD, PhD, and the senior author is A. Thomas Look, MD, both from Dana-Farber. Using high-powered gene-sequencing technologies, Look and his colleagues found five never-before-identified mutations in ALK in 8 percent of the neuroblastoma tumor samples studied. The mutations were all in a portion of the gene responsible for the enzymatic activity of the ALK "receptor," which transmits growth and survival signals to the cell. Some of the mutations give neuroblastoma cells the ability to proliferate even without the molecules that normally activate the receptor in a highly controlled way, the researchers found. To see whether such haywire growth can be stopped, investigators mixed a powerful ALK-blocking molecule into batches of test cells whose ALK receptors harbor each of the newly discovered mutations. The small molecule inhibitor, TAE684, halted proliferation and brought on the death of cells with the most common mutation, designated F1174L, as well as cells with another of the mutations. When investigators treated human neuroblastoma cells harboring the F1174L mutation with TAE684, the responses were just as dramatic as they had been in the test cells. The results were confirmed when researchers used a second technique for shutting down ALK genes with the F1174L mutation. "Our timing is good because there is a new inhibitor of the ALK receptor that is currently showing promise in clinical trials in adults, and which should be available soon for clinical trials in children," said Look. "We are very hopeful that this drug will have activity in children whose tumors have these mutations. More studies are needed, but we are excited by the possibility that this drug and others like it will represent a major step forward for some children with neuroblastoma." Dana-Farber Cancer Institute |
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| Related Neuroblastoma Current Events and Neuroblastoma News Articles Weizmann Institute Scientists Discover A New Protein Partnership That Leads to Pediatric Tumor Regression Why are some pediatric cancers able to spontaneously regress? Prof. Michael Fainzilber and his team of the Weizmann Institute's Biological Chemistry Department seem to have unexpectedly found part of the answer. PET Can Help Guide Treatment Decisions for a Common Pediatric Cancer A new study published in the August issue of The Journal of Nuclear Medicine shows that positron emission tomography (PET) is an important tool for depicting the extent of neuroblastoma in some patients, particularly for those in the early stages of the disease. Protein That Promotes Cancer Cell Growth Identified Scientists at Burnham Institute for Medical Research (Burnham) have found that the Caspase-8 protein, long known to play a major role in promoting programmed cell death (apoptosis), helps relay signals that can cause cancer cells to proliferate, migrate and invade surrounding tissues. U of M Researchers Find Childhood Cancer Risk Rises with Mother's Age Research from the Masonic Cancer Center, University of Minnesota indicates that a baby born to an older mother may have a slightly increased risk for many of the cancers that occur during childhood. Variations in 5 genes raise risk for most common brain tumors Common genetic variations spread across five genes raise a person's risk of developing the most frequent type of brain tumor, an international research team reports online in Nature Genetics. Genetic finding could lead to targeted therapy for neuroblastoma Researchers have identified a genetic glitch that could lead to development of neuroblastoma, a deadly form of cancer that typically strikes children under 2. Researchers identify gene that regulates tumors in neuroblastoma Virginia Commonwealth University researchers have identified a gene that may play a key role in regulating tumor progression in neuroblastoma, a form of cancer usually found in young children. New therapy enlists immune system to boost cure rate in a childhood cancer A multicenter research team has announced encouraging results for an experimental therapy using elements of the body's immune system to improve cure rates for children with neuroblastoma, a challenging cancer of the nervous system. Immunotherapy effective against neuroblastoma in children A phase III study has shown that adding an antibody-based therapy that harnesses the body's immune system resulted in a 20 percent increase in the number of children living disease-free for at least two years with neuroblastoma. Drug therapy reduces neuroblastoma tumor growth in pre-clinical investigation Researchers from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have discovered a new drug combination that significantly hinders tumor growth in neuroblastoma, a childhood cancer. More Neuroblastoma Current Events and Neuroblastoma News Articles |
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