Cancer is the most common cause of death due to disease in children. Neuroblastoma (NB) is an embryonal tumor which has a dismal outcome in patients with metastatic or relapsed diseases. Based on our previous experience in NB genomics and molecular imaging, we will utilize modern microarray technologies to identify the key molecular biomarkers that are differentially expressed the most in NB tumors vs. in BM. Next, we will validate the efficacy of these biomarkers in detecting minimal residual disease (MRD) of NB; their biological effects by using preclinical models; and their prognostic value by using clinical samples. Finally, we will use the preclinical models to develop targeted therapy to SPARCL1 and other targets selected from the newly identified biomarkers. Specific aims of this study include: 1. To identify the key biomarkers specific for metastatic NB using microarray and bioinformatic approaches. 2. To validate the efficacy of key biomarkers in detecting MRD of NB in bone marrow and peripheral blood samples and to compare the results with FDG and FDOPA PET imaging. 3. To verify the prognostic value of the key biomarkers in clinical NB patient samples. 4. To examine the biological effects of the key biomarkers on NB cells, xenografted mice, and transgenic mouse models. 5. To develop treatment approaches that target SPARCL1, a previously found biomarker in NB, and other key biomarkers of NB metastasis using preclinical models. Upon the completion of the project, we anticipate the following results: (1) The potential biomarkers of NB metastasis will be found out. (2) The biological and prognostic implications of these markers will be examined and validated. (3) The therapeutic effect of these biomarkers will be explored.
|Effective start/end date||8/1/17 → 7/31/18|
- bone marrow metastasis
- targeted therapy
- minimal residual disease
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