Our 2013 Childhood Cancer Research Grant cycle is now open. Visit pablove.org/grants/apply to download an application. Proposals are due March 1st, 2013.
2012 Childhood Cancer Research Grants
We are proud to announce the funding of six innovative research projects that we believe will make a real, lasting effect on childhood cancer treatment. Here’s more information about the projects our Board of Directors and esteemed Scientific Advisory Committee selected for funding for our 2012 Childhood Cancer Research Grants:
Role of the GAB2-SHP2 network in childhood neuroblastoma pathogenesis
Shizen Zhu, MD, PhD
Dana-Farber Cancer Institute
This project addresses the role of the SHP2 pathway in neuroblastoma (NB) using a zebrafish model. In a high-profile Cancer Cell paper earlier this spring, Dr. Zhu was able to generate NB in zebrafish, raising the possibility that new agents could be tested in zebrafish NB prior to translation to human NB. Here, the applicant will explore the role of SHP2, a gene involved in ~4-5% of human NB, on tumor formation in zebrafish. The proposal is hypothesis-driven and will test the impact of SHP2 expression on several aspects of NB tumorigenesis, including proliferation and apoptosis. The structure-function approach is logical, and will likely yield important insights into NB pathogenesis. Observations derived from these studies could eventually lead to the identification of pathways that could be targeted with novel therapeutics.
Phase I/II clinical trial evaluating NK cell immunotherapy in relapsed and refractory pediatric solid tumors
Monica Thakar, MD
Children’s Hospital of Wisconsin & Medical College of Wisconsin
This is a Phase I/II clinical trial in pediatric patients with relapsed or refractory solid tumors (Wilms, neuroblastoma, Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, other soft-tissue tumors, hepatoblastoma, malignant rhabdoid tumors, other renal tumors, and Central Nervous System tumors). Currently, there are very few therapeutic options for many of these diseases when patients relapse. Dr. Thakar proposes a novel treatment approach that combines allogeneic bone marrow transplantation with an infusion of donor natural killer (NK) cells. This proposal will take advantage of the ”graft vs. tumor” effect, using the stem cell donor’s immune system to help combat very resistant disease. This approach has been evaluated in an ongoing study in patients with refractory leukemias, and is well-tolerated.
Elucidating Epigenetic Mechanisms for Therapeutic Targeting in Aggressive Pediatric Cancers
Boris Wilson, PhD
Dana-Farber Cancer Institute
For this project, Dr. Wilson will focus on the SWI/SNF complex that regulates cellular growth through its effect on the reading of DNA and that can lead to tumors when altered. Currently, it is not clear how alterations in this complex specifically drive the development of tumors. Dr. Wilson will directly test each of the components of this complex to better understand how it functions and how misregulation leads to cancer, which will test his novel and intriguing hypothesis that the complex is altered but still functional when mutated. This work will contribute to our understanding on rare pediatric cancers called malignant rhabdoid tumors that contain alterations in the SWI/SNF chromatin remodeling complex.
Develop Small Molecule Yap Inhibitors to Treat Childhood Cancer
Chungling Yi, PhD
Lombardi Cancer Center at Georgetown University
This proposal will use state of the art high-throughput screening technologies, both in vitro and in silico, to identify small molecule inhibitors of the YAP oncoprotein. YAP (YES-associated protein) is a growth promoting protein that is highly active in embryonic growth and its inactivation is critical for proper regulation of organ size. It is negatively regulated by a recently described tumor suppressor pathway called HIPPO. Genes that encode for members of the HIPPO pathway are frequent targets of mutation in cancer including NF2, which is mutated in 10 percent of patients with neurofibromatosis. Additionally, over-expression and inappropriate activation of YAP has been detected in numerous human cancers including Ewing sarcoma where it promotes tumor growth. Successful targeting of YAP may have potential therapeutic benefit for a wide range of pediatric tumors that have mutations leading to inactivation of HIPPO and activation of YAP.
We are also proud to renew funding for the following projects based upon excellent progress reports:
Phase 1 Dose Escalation Study of Sorafenib and Irinotecan Combination Therapy in Pediatric Patients with Relapsed or Refractory Solid Tumors
Holly Meany, MD
Children’s National Medical Center
This early phase clinical trial combines cytotoxic chemotherapy with molecular-targeted treatment in children with relapsed solid tumors, including Wilms Tumor. Wilms Tumor is the most common form of kidney cancer in children, often occurring in kids under the age of five. This trial may help continue to raise the bar of childhood cancer survival and has shown excellent progress after it’s first year.
Identification of Clinical Biomarkers of Wilms Tumor Using High Accuracy Mass Spectroscopy Urine Proteome Profiling
Elizabeth Mullen, MD
Dana-Farber Cancer Institute
This project continues to investigate the development of urine tests to predict outcomes in children with Wilms Tumor using cutting edge technology called proteomics. This may lead to further understanding of why Wilms Tumor behaves the way it does and will be of particular importance in those who relapse or suffer from anaplastic (unfavorable) disease.
Read the full Press Release…