Acceleration Initiative – An Outcome Driven Approach
Through the Acceleration Initiative (AI), launched in 2013, CureSearch has broken new ground in the children’s cancer research field — allowing us to transcend the barriers of a broken system and establish a new pathway to end childhood cancer.
The $10 million Acceleration Initiative elicits and invests in the best, most innovative pediatric cancer research. We bring together the brightest thought leaders in the field today to agree to the areas of greatest challenge in children’s cancer research. We then target specific grants to resolve those challenges and accelerate the search for cures.
All AI projects are marked by the following characteristics:
- Highly innovative with the potential to break new ground in the field
- Probability of clinical application (i.e. ready to reach patients within 3 years — an accelerated time frame)
- Help overcome scientific and therapeutic roadblocks to speed up the delivery of promising interventions (i.e. transcends a broken system to end childhood cancer)
Acceleration Initiative – Three Phases
The Acceleration Initiative has been implemented in three phases. The $5 million AI-1 portfolio, initiated in 2013, is focused on three discreet challenges facing the children’s cancer research field: halting metastatic disease; addressing refractory disease and treatment toxicity; and developing a novel therapeutic approach.
AI-2 began in March 2015 in partnership with the Switzerland-based Rising Tide Foundation for Clinical Cancer Research. The $2 million AI-2 International Grand Challenge Awards address two critical challenges in pediatric cancer treatments: creating novel approaches to children’s cancer survivorship; and accelerating the delivery of new therapeutic agents for pediatric patients.
AI-3 began in May 2016 with up to $2M available to address three critical grand challenges in pediatric cancer: 1) Validation of novel biomarkers to improve clinical outcomes for high-risk pediatric cancers, 2) Novel approaches for complementary, combination therapies targeting high-risk pediatric cancers, and 3) Accelerating novel therapeutics/innovative technologies developed for adults into the pediatric cancer realm.
Acceleration Initiative – Grant Recipients
Acceleration Initiative 3 (2016-2019)
One Acceleration Initiative 3 award was announced in November 2016 that focuses on validation of novel biomarkers to improve clinical outcomes for high-risk pediatric sarcomas.
Challenge: Validation of Novel Biomarker to Improve Clinical Outcomes for High-Risk Pediatric Cancers
Investigator: Andrew Kung, MD, PhD
Institution: Memorial Sloan Kettering Cancer Center
Project Title: “Integrative Analysis to Identify New Therapies for Pediatric Sarcoma“
Although outcomes for children with cancer steadily improve, survival of children with high-risk sarcoma has remained unchanged over the last 20 years. For these cancers (rhabodomyosarcoma, Ewing sarcoma, ostesarcoma) the five-year survival rate ranges from 20-40%. Advances in genomics have led to a much greater understanding about the genetic causes of childhood sarcomas, yet that knowledge has not translated to benefit children in the clinic. A major barrier to progress is that the genetic drivers of childhood sarcoma are not amenable to direct drug targeting. That is because many of the genes that drive pediatric sarcomas are transcription factors, proteins that activate gene expression. Transcription factors lack regions that can be easily used to tailor a specific drug (targeted therapy). There is therefore a pressing unmet need for new methods to identify vulnerable targets in childhood sarcomas.
Dr. Andrew Kung at Memorial Sloan Kettering, through a $1.26M Acceleration Initiative Award, has developed a new method to assess the entire signaling network within cancer cells, and to identify the critical signaling nodes, or Master Regulators (MRs), that drive malignancy. Dr. Kung’s team is using a systems biology approach, where molecular profiling is paired with bioinformatics to identify the key MRs. They have successfully used this method to identify critical MRs in a number of adult cancers. They will use this approach to analyze single patient samples from children with high-risk sarcomas, identify MRs and then identify drugs that target the activity of the MRs. Read more
Acceleration Initiative 2 (2015-2018)
Two new Acceleration Initiative grants were announced in October 2015 focusing on delivering novel therapies for high-risk pediatric brain cancers and acute myeloid leukemia (AML).
Challenge: Accelerating the Delivery of Novel Therapeutic Agents
Investigator: Richard Gilbertson, MD, PhD
Institution: University of Cambridge, Cambridge, England
Project Title: “Targeted Therapies for High-Risk Pediatric Brain Tumor Subtypes“
Brain cancers are the most common solid tumors in children, accounting for 20% of all childhood cancers. For high-risk cancers, standard treatment regimens (surgery, chemotherapy, radiation) are not effective, with high rates of relapse and poor survival outcomes. The goal of Dr. Gilbertson and his team is to develop specific treatments for especially lethal brain cancers in the hopes of improving the outcome for patients. The team is testing the novel hypothesis that “high risk subtypes of pediatric brain tumors are biologically distinct, rendering them susceptible to different chemotherapies that require subtype-specific treatments”. Using genomic analysis of different brain tumor subtypes, Dr. Gilbertson and his team hope to identify novel targeted therapies for each type of brain cancer. They will test a total of 30 compounds that are a combination of FDA approved and new compounds. 2-3 lead compounds for each subtype will be tested in “preclinical trials”. They will combine standard of care with the novel drug therapies in mouse models of each high-risk pediatric brain tumor. By using such a protocol, the researchers hope to better replicate the treatment regimen of patients in the clinic to produce a more effective therapy. The ultimate goal is to inform clinical practice with these combined treatment approaches to cure high-risk brain tumors that have previously not been treatable. Read more
Challenge: Accelerating the Delivery of Novel Therapeutic Agents
Investigator: Maria-Grazia Roncarolo, MD
Institution: Stanford University
Project Title: “Cell Therapy Methods to Improve AML Patient Outcome Post Allo-HSCT“
Acute myeloid leukemia (AML) is a type of blood cancer that accounts for one-fourth of all childhood leukemias. Aggressive chemotherapy is the current treatment for AML. To replace damaged cells, a bone-marrow or stem cell transplant is frequently given to patients. Allo-HSCT (allo = from a donor; HSCT= hematopoietic stem cell transplant), has two major effects. The therapeutic benefit is to kill the leukemia. An undesirable effect is a toxic reaction called Graft versus Host Disease (GvHD) where the donor cells attack the patient’s cells. GvHD is often fatal and is a leading cause of AML patient mortality. Dr. Maria-Grazia Roncarolo and her team, at Stanford University, have developed a novel cell based therapy to optimize GvL and minimize GvHD that will ultimately be tested in a Phase 1 clinical trial. The hope of Dr. Roncarolo and her team is that this new therapy will dramatically reduce mortality and improve the long-term survival of pediatric AML patients. Read more
Acceleration Initiative 1 (2013-2016)
The first three grants in the AI-1 portfolio were announced in September 2013 and are focused on three discrete challenges facing the children’s cancer research field:
Challenge: Halting Metastatic Disease
Investigator: Mary Beckerle, PhD
Institution: University of Utah – Huntsman Cancer Institute
Project Title: “Epigenetic Regulation of Ewing Sarcoma: A Novel Approach to Influence Tumor Phenotype and Metastasis“
Ewing sarcoma is the second most common bone cancer in children — yet it is a challenging cancer to treat. Typically, by the time it is diagnosed, the cancer has spread. Many patients also relapse after initial chemotherapy and surgeries. Yet, the Huntsman team has made great strides in reaching a life-saving breakthrough for Ewing Sarcoma patients. By targeting and inhibiting the growth of a specific enzyme on which the cancer feeds, the team expects to also be able to halt the growth and spread of disease. The treatment that may result will be far less toxic than conventional therapy, and may provide increasing returns by proving effective for other cancers in both children and adults. This kind of exponential impact is a hallmark of Acceleration Initiative research, and demonstrative of how CureSearch intends to end childhood cancer by moving treatment quickly from bench to bedside. Read more
Challenge: Addressing Refractory Disease/Treatment Toxicity
Investigator: William Weiss, MD, PhD
Institution: University of California – San Francisco
Project Title: “Overcoming Resistance in High-Risk Medulloblastoma“
CureSearch projects address difficult to treat cancers to improve the odds even for disease types and populations that haven’t shown as much improvement as the field as a whole. This project hopes to improve outcomes for patients who do not respond to treatment for high risk medulloblastoma. Survival rates for this high risk disease are 60-65%. If a child is an infant when diagnosed and the cancer is localized, survival rates can be as low as 30-50%. Recently, Dr. Weiss’ team uncovered parallels between genes involved in medulloblastoma and genes in other, more common cancers. As a result, they have been able to apply insights from those more common cancer treatments to improve therapies for brain tumors. This work promises to identify compounds that are already in the clinic or about to enter trials, or FDA approved, and re-purpose them to better treat medulloblastoma. Read more
Challenge: Developing a Novel Therapeutic Approach
Investigator: Kathleen Sakamoto, MD, PhD
Institution: Stanford University
Project Title: “Development of CD47 Monoclonal Antibody Therapy for Pediatric Tumors“
Dr. Sakamoto and Dr. Weissman at Stanford University have been working on a novel treatment for malignant tumors in children, with a focus on pediatric brain tumors. They have developed an innovative treatment approach to harness the body’s own immune system to fight cancer. The project intentionally includes an analysis of not just whether the treatment was effective, but what side effects it produced, and at what dosage the treatment could minimize negative impact on patients. The treatment has moved into adult clinical trial phase, and is being explored for efficacy among additional cancer types.
CureSearch is committed to research that has the highest probability of saving children as fast as possible. Due to a significant delay in the launch of the pediatric clinical trials, CureSearch discontinued funding this project in April 2016. Read more