The Matthew Larson Pediatric Brain Tumor Foundation awards annualgrants through a competitive application and review process.  Each yearsubmissions are thoroughly evaluated by the Medical Advisory Committeeand written recommendations are submitted to the Board of Directors forapproval.  The information materials for grant submission and theapplication are available on the website.

The 2010 grants were awarded for the following investigators:

1) Rachid Drissi, PhD, Assistant Professor at the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio. . The proposal is titled: Telomerase: A Therapeutic Target in Pediatric Brain Tumors.

The outcome for children with may brain tumors remains poor. Current standard therapy for children with high-grade glioma that includes radiotherapy has devastating side effects on the child’s life. The long-term goal of this pilot study is to improve the efficacy of radiation while minimizing its side effects. This project is design is to use radiation concurrently with a compound that sensitizes cancer cells to radiation therapy. This combination therapy is expected to be more effective at lower radiation doses and therefore will minimize the side effects.

2) Dr. Jason Fangusaro, MD, assistant professor at Children's Memorial Hosiptal in Chicago, IL, and Vidya Gopalakrishnan, PhD, assistant professor at MD Anderson Cancer Center in Houston, TX. Their proposal is titled: RE1 Silencing Transcription (REST) Factor as a Prognostic Factor and Therapeutic Target for Medulloblastoma.

Currently, the prognosis for Medulloblastoma in children is based on non-specific factors like age of the child and spread of the tumor. This study aims to find out if RE1 Silencing Transcription Factor (REST) could be used as a prognostic factor. REST helps block the generation of neurons from stem cells until the appropriate time in the cell life and recently been found in human Medulloblastoma samples. This study will examine the relationship between REST and Medulloblastoma and will look for opportunities to target REST expression.

3) Dr. Christopher Pierson, MD, PhD, assistant professor at Nationwide Children’s Hospital in Columbus, OH. The proposal is titled: Id Proteins in MedulloblastomaMedulloblastoma is the most common malignant childhood brain tumor.

Id proteins are abundant in many types of cancers but minimal or absent in normal cells. These proteins are important in cell proliferation, survival and invasion of malignant cells and are therefore an appealing anti-tumor target. This project looks to evaluate the role of Id proteins in Medulloblastoma and the feasibility of targeting them as a new treatment approach.

4) Angela Sievert, MD, MPH, instructor at the Children’s Hospital of Philadelphia in Philadelphia, PA. The proposal is titled: Targeting Activating BRAF Mutations in Pediatric Brain Tumors

Gliomas are the most common type of brain tumor in children and the long term prognosis can be favorable if the tumor can be completely removed. Treatment options are limited for the many children with unresectable or recurrent tumors. If effective, targeted therapies could be directed against specific biochemical or cellular abnormalities of these tumors. Mutant BRAF activation is a hallmark of pediatric gliomas and therefore a possible target. This study aims to test a panel of BRAF inhibitors in cell lines and mouse models to identify which are most promising therapies for pediatric gliomas.

One of the 2009-2010 grants were awarded for the following investigators:

Current radiation and chemotherapy treatments have increased the 5-year survival rate to ~80% for children with brain tumors. These children are at a high risk of developing learning and memory deficits, psychological and behavioral problems, and secondary malignancies. At this time, more than 250,000 children in the US are already at risk of developing these conditions and/or are presently experiencing mild to severe problems with school performance, the ability to hold a job, and interactions in social settings. There are no long-term successful treatments for children with radiation-induced brain injury. Data from our lab suggest that fenofibrate not only inhibits both whole brain radiation-induced inflammation and the decrease in neurogenesis in adult rodents, but it also can kill brain tumor cells in tissue culture. It is well known that many treatments that work in adults do not work in children or are much more dangerous to children. However, until now, there has been no good animal model for studying treatments for pediatric radiation-induced brain injury. The successful completion of the proposed specific aims in this grant offers not only the promise of finding a treatment to overcome the late effects that occur in children surviving brain cancer, but it will also provide the data to submit a competitive NIH grant proposal to continue the search for treatments that will improve the quality of life for the survivors of childhood brain cancer.

The  2007-08 grants were awarded for the following investigators:

1)      Drs. Oren Becher and Rosandra Kaplan from MemorialSloan Kettering Cancer Center in New York City.  Their proposal istitled:  Stromal Contribution of Bone Marrow Progenitors inMedulloblastoma. 

Meduloblastomas are brain tumors that arise in the cerebellum ofchildren.  Using animal models, this study examines whethermedulloblastomas contain cells that originate from the bone marrow. Recently, it has been observed that in adults, bone marrow derivedcells contribute to the formation of tumor blood vessels and assisttumor cells to invade normal tissue.  These researchers hypothesizethat these bone marrow derived cells act the same way in children’sbrain tumors.  Medulloblastoma cancer stem cells reside near bloodvessels and are more resistant to treatment with radiation andcisplatin.   Cells derived from the bone marrow may also be moreresistant to such treatment and may play a role in supporting thecancer stem cells.  In this study the researchers will use drugs thatinhibit bone marrow derived cells of medulloblastoma-bearing mice toassess if medulloblastoma tumor growth will be affected.  They will usethese inhibitors to determine if they increase the effectiveness ofradiation and chemotherapy.  They will also study the number of bonemarrow derived cells in the blood and cerebrospinal fluid of childrenwith brain tumors to determine if the number of these cells correlateswith the stage or tumor recurrence.  They hypothesize that drugs thatcan block bone marrow derived cells are potential novel treatments forchildren with brain tumors.

2)      Dr. Mark Kieran from Dana-Farber CancerInstitute/Harvard University in Boston.  His proposal is titled:  PhaseI Study of AdV-tk+ Prodrug Therapy in Combination with RadiationTherapy for Pediatric Brain Tumors

Childhood brain tumors called gliomas – those that arise in the glialcells – typically have a poor outcome.  Patients suffering from thisdisease usually survive for only a short number of months, soinnovative approaches to treatment are critical.  .  This study is aPhase I clinical trial in which pediatric patients’ gliomas will beremoved surgically, and a gene therapy vector, AdV-tk, will be injecteddirectly into the tumor site.  In the days that follow, patients willreceive prodrug and standard radiotherapy; standard chemotherapy may beused as well.  This approach will allow simultaneous targeting of thetumor with multiple methods.  This multiple method therapy has beentested using animal models and has been successfully used in adultswith brain tumors and other cancers.  This combination therapy showsgreat promise as an improved form of treatment for children with braintumors.

3)       Dr. Joseph Lasky from UCLA in Los Angeles.  His  proposal is titled: Immunotherapeutic Targeting of Stem Cells in Pediatric Brain Tumors

Although surgery, chemotherapy, and radiation therapy work in somecases of childhood gliomas and medulloblastomas, the devastating sideeffects of these therapies and relative lack of efficacy necessitatethe development of novel, targeted therapies for the developing brain. In this study, the research looks to harness the power of a person’sown immune system to fight these tumors.  The researchers will attemptto identify immunogenic proteins expressed by the brain tumor stem cellpopulation.  The genes, Bmi-1, SOX2, MELK, and FoxM1 have been shown toplay critical roles in cancer growth.  T-cells which are capable ofproliferating and activating in response to these proteins will then betested against cell lines generated from pediatric tumor samples and inanimal models.  The results will be used to develop individualizedvaccines for pediatric patients with brain tumors.