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Philadelphia, PA (June 4, 2019) – Alex’s Lemonade Stand Foundation (ALSF) has partnered with The ChadTough Foundation to support research in Diffuse Intrinsic Pontine Gliomas (DIPG). ALSF and ChadTough share a vision of funding childhood cancer research to ultimately find cures for all children with cancer.
The mission of The ChadTough Foundation is to inspire and fund game-changing research to discover effective treatments for pediatric brain cancer, with an emphasis on DIPG. A highly aggressive and difficult-to-treat brain tumor, DIPG is found in the pons of the brain stem. Children are typically diagnosed between the ages of 5-7 with around 300-350 new cases per year in the United States. The median survival rate is 9 months from diagnosis, and long-term survivors total less than 1%. DIPG is responsible for 15% of all pediatric cancer deaths in the US each year.
The ChadTough Foundation was established when Chad Carr passed away at just five-years-old after bravely fighting DIPG for 14 months. His parents were bewildered with the realization that the standard of care for DIPG had not changed in over 40 years due to a variety of factors including lack of tissue to study, the rarity of the disease and lack of funding for childhood cancer (approximately 4% of the taxpayer-funded National Cancer Institute’s annual budget is directed toward pediatric cancer as a whole).
The ChadTough Foundation will be supporting two grants with Alex’s Lemonade Stand Foundation: an Innovation Grant for Dr. Wolf-Dietrich Heyer of University of California, and a Reach Grant for Dr. Eric Raabe of The Johns Hopkins University School of Medicine.
Dr. Heyer’s study aims to create a drug for high-grade brain cancers that differentiates cancer cells from normal cells by targeting biological processes unique to cancer cells in a specific patient. This strategy of personalized, or precision medicine, creates a situation that kills only tumor cells, but not normal cells. Dr. Eric Raabe anticipates finding new drugs that can be combined with the drug TAK228 in phase II studies for patients with relapsed or refractory pediatric brain tumors.
A full description of the project is below.
For more information about Alex’s Lemonade Stand Foundation’s charity partnerships, visit AlexsLemonade.org/grants/charity-partners.
Targeting the ALT Pathway to Induce Synthetic Lethality and Treat Poor Outcome Pediatric Tumors
Wolf-Dietrich Heyer, PhD – University of California, Davis
The fundamental paradigm of cancer therapy is moving from conventional therapies which poorly differentiate cancer cells from normal cells to targeting biological processes which are unique to cancer cells in a specific patient. This strategy, termed personalized or precision medicine, targets a tumor-specific Achilles heel creating a situation that kills only tumor cells, but not normal (non-tumor) cells. We have identified such a tumor-specific vulnerability in a significant fraction of pediatric brain and bone cancers and propose to isolate inhibitors of the target MUS81 to exploit this tumor liability. Moreover, the normal function of MUS81 suggests that its inhibition will make conventional chemotherapy used to treat these cancers more effective. High-grade brain cancers or bone cancers of children that have spread from the primary tumor site are in desperate need of more effective treatment options.
Our project represents the earliest steps in drug development and we have two experienced pediatric oncologists on our team who will offer specific clinical perspective and expertise right at the earliest stage. Drug development is a long-term project, but through a serendipitous finding we also have the potential to repurpose an existing approved drug to significantly speed up the process. One specific attraction of our approach is that the treatment we envision is designed to be specific for the tumor cells and sparing of normal cells, which should lead to less side effects and less long-term adverse consequences, which are important considerations in particular for young cancer survivors and their quality of life.
Identifying a Therapeutic Partner for TAK228 for Pediatric Phase II Brain Tumor Studies
Eric H. Raabe, MD/PhD – The Johns Hopkins University School of Medicine
The goal of this proposal is to find new drugs that work together to kill pediatric brain tumor cells. As part of a previous Alex’s Lemonade Stand Foundation project, we found that a drug called TAK228 could kill pediatric brain tumor cells. This drug gets into the brain well and is currently in clinical trials in adults for breast and other cancer types. We found that TAK228 works well with some therapies we currently use in pediatric brain tumors. But those therapies may be too toxic for patients who have relapsed or refractory disease and who have already received heavy doses of chemotherapy and radiation.
We now propose to use our knowledge of the biology of TAK228 as well as the ways that cancer cell metabolism differs from normal cells to find new agents that could combine with TAK228 to kill pediatric brain tumor cells and spare normal cells. TAK228 is currently in the planning stages for a US-government-funded phase I study in pediatric brain tumors. At the end of this grant, we anticipate that we will have discovered at least one new drug that can be combined with TAK228 in phase II studies for patients with relapsed or refractory pediatric brain tumors.
Dr. Raabe’s project is also supported by Flashes of Hope and Closer to the Cure Hero Fund, in conjunction with Alex’s Lemonade Stand Foundation.
About Alex’s Lemonade Stand Foundation
Alex's Lemonade Stand Foundation (ALSF) emerged from the front yard lemonade stand of 4-year-old Alexandra “Alex” Scott, who was fighting cancer and wanted to raise money to find cures for all children with cancer. Her spirit and determination inspired others to support her cause, and when she passed away at the age of 8, she had raised $1 million. Since then, the Foundation bearing her name has evolved into a national fundraising movement. Today, ALSF is one of the leading funders of pediatric cancer research in the U.S. and Canada raising more than $150 million so far, funding nearly 1,000 research projects and providing programs to families affected by childhood cancer. For more information, visit AlexsLemonade.org.
About The ChadTough Foundation
The ChadTough Foundation inspires and funds game-changing research to discover effective treatments for pediatric brain cancer, with an emphasis on Diffuse Intrinsic Pontine Glioma (DIPG), which has been underfunded, compared to most cancers. Founded in 2015 in memory of Chad Carr, the Michigan-based Foundation is approaching nearly $5 million in grants for pediatric brain tumor research. The Foundation maintains a vision of a day when DIPG and other brain cancers can be survivable for children. For more information, visit www.chadtough.org.