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Tyrosine Kinase Mutation Discovery in Neuroblastoma.

Dana-Farber Cancer Institute
Matthew Meyerson, MD, PhD
Grant Type: 
Innovation Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Neuroblastoma is the most common tumor of early childhood outside of the brain. Despite efforts to improve chemotherapy and radiation treatment, few patients with advanced diseases are cured or even achieve long-term survival. The completion of the human genome project now offers new opportunities to understand neuroblastoma at the genetic level. Such understanding in turn could lead to the development of novel therapies.

Linking genetic alterations in cancer to therapeutics is a new paradigm for cancer treatment and has recently achieved multiple successes, such as the treatment of chronic myeloid leukemia with imatinib (Gleevec). Because there are many successful anti-cancer drugs that target one family of enzymes, the tyrosine kinases, we have chosen to focus our discovery effort on this enzyme family.

By determining the DNA sequence of the known tyrosine kinases and other candidate genes in neuroblastoma samples, we propose to generate a master list of targets for directed therapy. Small molecule inhibitors can then be developed for those targets identified in such an effort, or, if approved tyrosine kinase inhibitors already exist, those agents might enter clinical trials for neuroblastoma on an accelerated basis. Mutation screening of the tyrosine kinases and other select genes is an important step towards understanding the genetic basis of neuroblastoma.