Scientists close in on method to fight deadly childhood cancerOctober 16, 2008GAINESVILLE, Fla. - A multicenter team of researchers, including scientists from the University of Florida, has discovered a way to potentially block the growth of neuroblastoma, a type of cancer responsible for 15 percent of all cancer deaths in children. Working with human cell lines and tissue samples, researchers describe in Thursday's (Oct. 16, 2008) online issue of Nature how they were able to short-circuit genetic processes that apparently contribute to neuroblastomas - tumors that arise from the developing nervous system in children and often appear in the abdomen, chest or neck. Concentrating on a gene known as ALK, the scientists used a small-molecule inhibitor - a technique common to many drugs - to block abnormalities that apparently cause neuroblastomas. Neuroblastomas are extremely rare, appearing in about 600 patients annually in the United States, according to the National Institutes of Health. About half of the patients with neuroblastoma are diagnosed before the age of 18 months. In 40 percent of cases, the cancer has spread to other parts of the body by the time doctors discover it. Treatment usually involves surgery, chemotherapy and radiation, and transplantation for high-risk patients. "We need to find a home run for these kids," said Wendy B. London, Ph.D., a research associate professor of epidemiology, biostatistics and health policy research at the UF College of Medicine and a member of the UF Shands Cancer Center. "A targeted therapy to treat patients with ALK mutations would be a real breakthrough." Led by Dana-Farber Cancer Institute researchers Rani E. George, M.D., Ph.D., an assistant professor of pediatrics at Harvard Medical School, and A. Thomas Look, M.D., a professor of pediatrics at Harvard, the scientists analyzed the ALK gene in 94 tumors representative of general neuroblastomas and 30 neuroblastoma cell lines. Scientists discovered that ALK abnormalities in a subset of neuroblastoma cells appear to interfere with the natural cell-death processes. Furthermore, they found some of the ALK mutations were sensitive to a tiny organic molecule known as TAE684, a discovery that may be useful in efforts to create drugs to staunch cancer growth. In addition, researchers used gene-transfer techniques to initiate ALK-related cancer in rodent cells. These transduced neuroblastomas also appear vulnerable to the small molecule, known as an ALK inhibitor. The tumor samples were obtained from the Children's Oncology Group Neuroblastoma Tumor Bank. COG is a NIH/National Cancer Institute cooperative research coalition that conducts pediatric cancer clinical and biological trials, including specimen collection and statistical analyses. The University of Florida is one of three sites of the COG Statistics and Data Center, where the study design, data collection and statistical analyses of the data take place. The current findings dovetail with the recent discovery of the role of ALK mutations in both inherited and non-inherited versions of neuroblastoma published by researchers from The Children's Hospital of Philadelphia on Aug. 24 in Nature. "This research group looked at neuroblastoma in a totally different and complementary way to ours and came up with similar results, validating the role of ALK mutations," said pediatric oncologist Yael P. Mosse, M.D., of The Children's Hospital of Philadelphia. "A unique aspect of their work is they proved in a model system that these mutations can indeed be cancer-causing." With samples they had collected from families for the past 15 years, as well as additional data from the COG, Children's Hospital of Philadelphia scientists traced the genetic roots of many neuroblastomas to ALK mutations - findings that open the door to genetic screenings for the disease as well as possible therapies. Ultimately, researchers hope drug treatments can be developed to disrupt the cancer cell-signaling process. They are designing a clinical trial that would test small molecules against the cancer-causing mutations in the gene. "This is the epitome of translational research," said London, who is also the principal investigator of the COG Statistics and Data Center at UF. "We will use what we have learned about the sensitivity of ALK mutations to an ALK inhibitor and attempt to translate this knowledge to the development of targeted therapy for treatment of neuroblastoma patients in the clinic." University of Florida |
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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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