Presents the Friday Keck Center Teleconference*
Novel Targets in Pediatric Brain Tumors: From genomics to bedside
Ching C. Lau, Ph.D.,
Associate Professor of Pediatrics, Hematology/Oncology
Baylor College of Medicine
4:00 pm Friday
19th Jan. , 2007
(Refreshments at 3:45)
5.521 Levin Hall
Abstract: Despite advances in multi-modality therapy, the prognosis for malignant brain tumors in children remains poor. Even among the survivors, there are long-term neuro-cognitive sequelae of the disease compounded by the adverse effects of the therapies on the developing brain and other organ systems. Thus there is an urgent need to develop more specific therapies that can optimize survival while minimizing the toxic effects on the normal brain tissue. In the last few years, molecular genetic studies and genomic screening have provided a better understanding of the biology of medulloblastoma and helped identify novel therapeutic targets. These include the recognition of the involvement of the sonic hedgehog (SHH) pathway in the pathogenesis and the association of the over-expression of ERRB2 with poorer prognosis in medulloblastoma. Pre-clinical studies using inhibitors of SHH pathway and ERRB2 tyrosine kinase inhibitors are now underway. More recently the role of the Notch signaling pathway in medulloblastoma was also described and interference of this pathway with gamma secretase inhibitors leads to depletion of cancer stem cells in medulloblastoma. In addition, induced differentiation is also a very attractive therapeutic strategy since normal brain tissue will theoretically be spared the deleterious effects of cytotoxic agents. Some of the differentiation inducers under investigation include retinoids, phenyl butyrate, and other histone deacetylase inhibitors such as valproic acid. Furthermore, recent evidence suggest that telomerase plays a significant role in the pathogenesis of medulloblastoma and primitive neuroectodermal tumor and that inhibition of telomerase function represents a novel experimental therapeutic strategy. Similarly, high-grade gliomas in children were found to have increased activation of various signal transduction pathways involving the receptors of epidermal growth factor (EGFR) and platelet-derived growth factor (PDFGR) as well as the RAS pathway. Inhibitors of these pathways are now under intense investigation. Finally, novel methods used to exploit these potential targets such as nanotechnology and the development of cancer vaccine based on chimeric T-cell receptors against ERRB2 will also be discussed. ( http://www.txccc.org/content.cfm?content_id=966 )
