Childhood Cancer Research
Children’s Hospital of Philadelphia
3401 Civic Center Boulevard
Philadelphia, PA 19104
United States
The failure of cancer therapy to control tumor growth results from alterations in the pathways that control cell death decisions within tumors. Although the alterations cancer cells develop to gain a survival advantage are diverse, most ultimately lead to the disruption of death signals that should be Òturned onÓ when lethal stress is encountered. A family of Bcl2-homology (or BH) proteins are responsible for responding to these stressors to initiate a death signal when sufficient stress is present.
Although acute myeloid leukemia (AML) causes a substantial disease and treatment burden in both children and adults, the causes of AML and unsuccessful treatment are poorly understood. Currently, many scientists believe that naturally occurring genetic variation changes AML susceptibility and relapse risks. This application seeks to identify these specific genetic variations by searching throughout the genome with a genome-wide association study (GWAS). This research seeks to find these genetic changes with three specific aims.
Description not available.
The three specific aims of this project are to:
• Develop a tractable in vivo model for the monitoring of dynamic changes in neuroblastoma vascularization during tumor growth and in the context of chronic VEGF inhibition.
• Define optimal targets for synergistically enhancing the tumor growth delay mediated by anti-angiogenic effects of VEGF inhibition.
• Perform preclinical trials to define optimal dual angiogenesis inhibition strategies that are readily translatable to the clinic.
Precursor B-cell acute lymphoblastic leukemia is the most common cancer in children. In approximately 10% of patients with precursor B-cell ALL, the transcription factor E2A is involved in a chromosomal translocation. Three translocations have been identified: t(1;19), t(17;19), and inv(19), which fuse E2A to the genes PBX1, HLF, and FB1, respectively.
Background
Development of new anti-cancer drugs that can more precisely target childhood cancers offers the prospect of more effective therapy with fewer side effects. More than 70% of children diagnosed with cancer today are cured of their disease, but today’s therapy has both short term and lifelong side effects, and too many children still die from their cancer. A critical challenge is how best to combine new anti-cancer drugs with potentially curative but toxic chemotherapy.
Neuroblastoma is one of the most common and deadly solid tumors of childhood. Several genetic changes have been identified neuroblastomas that almost certainly contribute to the development or behavior of these tumors. We identified deletion of the short arm of chromosome 1 (1p) as a common and characteristic change of more aggressive neuroblastomas. Deletions in tumors generally suggest that some important tumor suppressor gene (TSG) in the commonly deleted region needs to be removed or inactivated to allow the tumor to develop or to be aggressive.
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