Childhood cancer isn’t just one disease—there are over a dozen types of childhood cancer and countless subtypes, each requiring specific research to develop the best treatment for every child. But in the last 20 years, only three new drugs have been approved that were specifically developed to treat children with cancer. Less than 4% of the National Cancer Institute’s budget is solely dedicated to childhood cancer research. By working closely with leading pediatric oncologists, we determine the most promising research to fund and create funding priorities to make the greatest impact for children with cancer.
Riley Hospital for Children/Indiana University health
Research Project: Establishment of the Jeff Gordon Children’s Foundation pediatric Oncology Physician Scientist Training Program
Grant Amount: $300,000
Jeff Gordon Children’s Foundation Pediatric Oncology Physician Scientist Training Program (POPSTP) will allow Indiana University Department of Pediatrics and Riley Hospital for Children to construct a multifaceted program aimed providing post-resident fellow trainees with extensive mentoring and training to ensure that diverse, highly trained scholars are available to carry out cutting-edge research in pediatric oncology.
A critical need exists for a robust supply of pediatric-focused clinician scientists with formal training. The recent National Institutes of Health (NIH) workforce report emphasized that the number of physician-scientist in the United States that are under age 50 has decreased by 50% from 2006 TO 2012. All available evidence indicates that this precipitous decline in the critical workforce is continuing.
Jeff Gordon Children’s Foundation POPSTP will be essential to successfully developing a cadre of pediatric physician scientists to become independent, productive academic pediatricians focused on improving outcomes for children and adolescents battling cancer.
Children’s Oncology Group (COG)
Research Project: EveryChild
Grant Amount: $382,500
Project:EveryChild includes a single research study conducted by the Children’s Oncology Group (COG) to capture the biology and outcome of every child diagnosed with cancer in the United States and COG’s affiliated countries. Participation is offered to every child diagnosed with cancer, no matter how “common” or rare the cancer may be. Key clinical data on disease presentation, therapeutic approach and outcome leverages the COG infrastructure. Biospecimens, including tumor tissue, host and when feasible parental DNA, are being stored at COG’s state-of–the-art biobank in Columbus, OH. These biospecimens will be made available to scientists across the country and around the world who are committed to finding better cures for children with cancer.
COG will additionally develop a complementary study to Project:EveryChild called Pediatric MATCH (Molecular Analysis for Therapy Choice) that will focus on children with relapsed cancer. Planning is well underway for the Pediatric MATCH protocol, which will not only allow researchers to gain significantly better knowledge of the genomic changes that occur in relapsed tumors but offer the opportunity for children with relapsed cancer to potentially receive a targeted new drug based on the molecular profile of their individual cancer. The study will allow the genomic study of biopsy specimens obtained at time of relapse and, for a subset of patients, match findings to a targeted drug that may be of benefit.
To date the Jeff Gordon Children’s Foundation has granted nearly $1.1 million to support Project:EveryChild, including $382,500 this year in order to secure Oragene® DNA collection kits for use with subjects and parents enrolled onto the study.
Children’s National Health System
Research Project: Leveraging Quantitative Proteomics to Develop More Precise & Less Toxic Treatments for Children Fighting Medulloblastoma
Grant Amount: $228,158
Few proteomic studies have been published on pediatric brain tumors, partly owing to the formidable complexity and dynamic nature of proteomes and the technical challenges of analyzing them. Dr. Brian Rood’s research team published the first study of the cerebrospinal fluid (CSF) proteome of medulloblastoma, using label free mass spectrometry to identify a presumed biomarker significantly reduced in medulloblastoma CSF samples. They have also published the only mass spectrometry- based quantitative proteomics study in medulloblastoma.
Prior funding from the Jeff Gordon Children’s Foundation (2014 grant) allowed the team to launch the first large- scale super-SILAC project in cancer research and put Dr. Rood’s team at the forefront of understanding of disease biology. The 2015 grant will add gene expression and methylation profiling to their existing SILAC-generated data. By conducting gene expression and methylation profiling, Dr. Rood’s team will be able to construct robust subgroup-specific protein interaction pathways that will provide a significantly enhanced picture of how proteins conduct the work of medulloblastoma cells. They will then use commercially available drugs to inhibit these pathways and determine their ability to inhibit tumor cell growth, induce cell death, and affect the chemical processes that maintain cancer cells’ functionality.
Dr. Rood’s team is taking an innovative approach to developing future treatments for medulloblastoma. Rather than following the typical drug screening process, which investigates tens of thousands of compounds at a time but rarely yields prospects for clinical use, they are instead focusing on screening the protein pathway targets responsible for the fundamental processes that make a medulloblastoma tumor cell capable of destructive growth.
Cincinnati Children’s Hospital Medical center
Research Project: Therapeutic Trial of the Immune Check Point Inhibitor Pembrolizumab with Decitabine in Relapsed Refractory Solid Tumors
Grant Amount: $200,000
Sarcomas are cancers that arise in connective tissues such as bone, muscle, or cartilage. Over 14,000 people are diagnosed with sarcoma in the United States each year. Notably, sarcomas comprise 21% of the solid tumors that affect children, and bone sarcomas are particularly common in young adults and adolescents. Therapy for most sarcomas typically consists of some combination of chemotherapy, radiation, and surgery. Although many patients with localized sarcoma can be cured, the vast majority of children, adolescents and young adults with metastatic or relapsed sarcoma will not survive their disease. Further, many survivors of childhood cancers experience chronic debilitating side effects of therapy.
Chemotherapy approaches to improve the cure rates in sarcoma have been exhausted and new approaches are needed. Manipulation of the patient’s immune system to kill tumor cells (immunotherapy) has been shown to be not only feasible, but very active in treatment of several adult malignancies, including melanoma and lung cancer. Using immunotherapy to treat sarcomas in young people has a strong rationale, as these cancers display unique targets that the immune system can recognize, resulting in death of tumor cells. Recently, laboratory investigations have identified the molecular mechanisms that allow cancer cells to evade the immune system. Tumor cells often evade the immune system by expressing a class of proteins that turn off normal immune cell functions, called immune checkpoints. When a cancer cell displays these immune checkpoints, normal immune cells are incapable of expanding into an army capable of killing the tumor.
New anticancer agents known as “check point inhibitors” block these signals, and are now being applied in a variety of settings, with dramatic responses seen in a variety of adult cancers. Immune checkpoint blockers are promising therapies for various cancers, but do not have lasting activity as a single drug treatment for many childhood, adolescent and young adult cancers because the tumors become resistant. The goals of this study are: (1) to identify the key mechanisms that cause resistance, (2) identify treatments in the laboratory that act in combination with checkpoint inhibitors to overcome resistance, and (3) conduct a phase 1/2 clinical trial to examine the safety and effectiveness of this combination therapy approach.