Touchdown: Neurobiology & Brain Tumor Program

    Tyler Rewis is no different than any other quarterback. He relies on his teammates to thwart the burly opponents who are intent on tackling him. But one thing sets this 11-year-old apart from other quarterbacks. Much of Tyler’s success is due to another team—a group of researchers and clinicians at St. Jude Children’s Research Hospital.

    When Tyler began complaining of headaches in the fall of 2003, his mom assumed he had sinus problems. But Diane Rewis soon learned that Tyler had a tumor in the part of the brain that gives him the coordination he needs to run plays and intercept passes. A surgeon offered Tyler’s family some sage advice. “He told us that if it were his child, he would take Tyler to St. Jude,” recalls Diane. “I said, ‘Well, then that’s where we’ll go.’”

    When they arrived in Memphis from Georgia, the Rewis family learned that a group of scientists and clinicians working in an area called the Neurobiology and Brain Tumor Program (NBTP) would run interference for the young quarterback in his attempt to beat medulloblastoma.

    Planning the plays

    The success of the NBTP depends on exquisite teamwork by scientists and clinicians across the institution. Led by Tom Curran, PhD, of Developmental Neurobiology and Larry Kun, MD, of Radiological Sciences, the NBTP is one of the largest pediatric brain tumor programs in the country. NBTP can rally a highly experienced, multidisciplinary team of health care specialists on behalf of children like Tyler.

    Researchers in the program are trying to discover changes in the genes and proteins that are responsible for initiating and guiding normal development of the nervous system. These scientists are also trying to find out what happens when things go awry. Meanwhile, clinicians are developing and testing new therapies based on drug treatments and irradiation to improve treatment of central nervous system tumors. A third group is investigating ways to improve intellectual and learning abilities among long-term survivors of pediatric brain tumors.

    Bench to bedside

    As leader of the NBTP’s Fundamental Neuroscience group, Curran has made significant contributions to understanding the molecular (protein) signals that drive the development of medulloblastoma, the most common malignant brain tumor in children. Curran recently showed that a drug called HhAntag could block a key signal driving medulloblastoma, and reverse this cancer in a laboratory model of the tumor. The finding could lead to development of a relatively non-toxic, oral medication that increases the likelihood of curing medulloblastoma, while reducing long-term side effects.

    Led by Amar Gajjar, MD, of Hematology-Oncology and Richard Gilbertson, MD, PhD, of Developmental Neurobiology, the NBTP’s Translational Research Group adapts discoveries made in the laboratory into life-saving and less-toxic treatments for children.

    Gilbertson and his colleagues discovered an overabundance of a protein called ERBB2 in children who have advanced metastatic (spreading) medulloblastoma and a relatively poor outcome. Gilbertson’s team also showed that a test for ERBB2 in the tumor cells might help doctors identify children who need a novel approach to treat their tumors; children without this ominous protein might benefit from a milder course of treatment that minimizes radiation’s long-term effects. In addition, these scientists have opened a unique clinical trial in which patients with recurrent brain tumors that express ERBB2 will be treated with a new drug that inhibits the protein’s activity.

    Medulloblastoma therapy

    Gajjar and Gilbertson also head the Medulloblastoma Research Group, which offers cutting-edge therapies based on the latest discoveries made at St. Jude. One ambitious clinical trial (SJMB03) seeks to develop genetic profiles of medulloblastomas that can predict how well an individual’s tumor will respond to therapy. Projects are designed to find safer and more effective ways to help physicians tailor therapies for individual patients and increase the success rate of treatment.

    NBTP also benefits from a program that turns laboratory discoveries into new investigational drugs. This drug discovery program, in place at St. Jude for the past two decades, served as the model for a national initiative funded by the National Cancer Institute. Designed to expand the number of drugs screened against childhood cancers, the program is being led by Peter Houghton, PhD, of Molecular Pharmacology.

    And St. Jude treatment doesn’t end with the last day of anti-cancer therapy. A team of researchers and clinicians in Behavioral Medicine study new psychological, pharmacological, and educational therapies aimed at minimizing learning problems among long-term survivors of brain cancer who are treated with wide field irradiation. In collaboration with Shawna Palmer, PhD, of Behavioral Medicine, SJMB03 is the nation’s first clinical protocol to adapt a randomized study design to a program evaluating long-term reading skills.

    From test tube to the end of treatment, NBTP is creating new knowledge and saving the lives of children with brain tumors. Tyler Rewis is a shining example of that effort. An academic honor student, the sixth grader spends his free time playing baseball, swimming, fishing and playing video games with his buddies. And—thanks to the efforts of the NBTP—Tyler knows that when he grows up he may just have a chance to play football for his favorite team, the University of Georgia Bulldogs. Now, that’s teamwork at its best.

    Reprinted from Promise magazine, Autumn 2005


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