ALSF announces grant award recipients of Crazy 8 Initiative in pediatric oncology

Alex's Lemonade Stand Foundation (ALSF), a nonprofit foundation devoted to finding cures for all children with cancer, announces grant award recipients of their Crazy 8 Initiative. The recipients will receive grants totaling more than $18.5 million, which is the single, largest funding commitment from ALSF to date.

The Initiative kicked off in the Fall of 2018 with a meeting that brought together more than 90 scientists from around the world to help define the research landscape in eight key areas of need in order to tackle major obstacles impeding progress toward cures for childhood cancer. Through a rigorous review process, ALSF received over 100 letters of intent from researchers that resulted in 83 full grant applications which were ultimately narrowed down to four projects that will work to accelerate the pace of new cure discovery.

Childhood cancer is the leading cause of death by disease in children, and the Crazy 8 Initiative is poised to change the trajectory of pediatric oncology. Grants from the Crazy 8 Initiative will fund research for innovative and rigorous approaches that directly address the most obstinate issues in pediatric cancer research. A key component of the Initiative is its approach in bringing cross-disciplinary scientists to work collaboratively in order to accelerate the pace of new cure discovery. For example, connecting neurologists and biologists with pediatric oncologists to work hand-in-hand in growing scientific discovery, while aiming to provide detailed roadmaps for hard-to-treat childhood cancers.

The Crazy 8 Initiative is vital because it orchestrates talent from around the world and creates collective solutions. Pediatric cancer research is at an incredibly pressing moment right now, and we're thrilled to be at the forefront of this progress--generating opportunities to turn competition into collaboration by bringing world-class researchers together. This initiative is monumental, and we know it will provide a tremendous impact globally in moving the needle for pediatric cancer research over the next five years."

Liz Scott, Co-Executive Director, Alex's Lemonade Stand Foundation

An overview of the awarded Crazy 8 Initiative projects including project investigators, key institutions, and cross-cutting technologies can be found below.

Yael P. Mossé, MD, of Children's Hospital of Philadelphia, and a group of investigators from various institutions are teaming up to create a drug that will target the transcription factor MYCN, which drives aggressive pediatric cancers such as neuroblastoma and medulloblastoma. They will employ cutting-edge technology called targeted degradation to design a drug that will trick the cancer cells to dissolve MYCN, leading to cancer cell death.

The team of investigators includes: John Maris, MD and Ophir Shalem, PhD, of Children's Hospital of Philadelphia; Seychelle Vos, PhD, MIT; Gwenn Hansen, PhD, Nurix Therapeutics; Martine F. Roussel, PhD, St. Jude Children's Research Hospital; Natalia Jura, PhD, Kliment A. Verba, PhD, and William A. Weiss, MD/PhD of University of California San Francisco; Martin Eilers, PhD and Elmar Wolf, PhD of University of Würzburg

Charles G. Mullighan, MBBS(Hons) MSc MD FRACP FRCPA, of St. Jude Children's Research Hospital is leading a team to tackle mutant transcription factors that drive acute leukemias and medulloblastoma, two leading causes of cancer-related death in children. Aberrant transcription factors are difficult to inhibit with traditional drugs, and that's where this team is focusing its efforts, utilizing a new technology called molecular glues to degrade previously undruggable transcription factors.

They will develop a library of molecular glues to screen for agents that are successful at killing acute leukemia or medulloblastoma cells. The team of investigators, all from St. Jude Children's Research Hospital, includes: M. Madan Babu, PhD, FRSC; Marcus Fischer, PhD; Jeffery M. Klco, MD/PhD; Paul A. Northcott, PhD; Zoran Rankovic, PhD; and Martine F. Roussel, PhD.

Led by Leonard Zon, MD, of Boston Children's Hospital, investigators are joining forces to use a new genetic fingerprinting technology to study how blood cancers, such as leukemia, arise in development. They aim to understand what types of blood stem cells lead to different forms of pediatric leukemia and which key gene and pathway disruptions can alter stem cell function and subsequently kill leukemia cells. Ultimately this will inform new drug development for therapies that will disrupt leukemic stem cells and not normal blood stem cells.

The team of investigators includes: Scott A. Armstrong, MD/PhD and Serine Avagyan, MD/PhD of Dana-Farber/Boston Children's Cancer and Blood Disorders Center; Fernando Camargo, PhD and Vijay G. Sankaran, MD/PhD of Boston Children's Hospital; Ross Levine, MD, Memorial Sloan Kettering Cancer Center; Juerg Schwaller, MD, University Children's Hospital and Department of Biomedicine, University of Basel, Switzerland; Jay Shendure, MD/PhD, University of Washington School of Medicine; Peter Campbell, MD/PhD, Wellcome Sanger Institute

Heinrich Kovar, PhD, of St. Anna Children's Cancer Research Institute, Vienna, Austria is leading a team to examine the developmental origins of malignant bone tumors, such as Ewing sarcoma and osteosarcoma. Using new single-cell genomics technology that examines single cells, as opposed to clusters of cells, and trans-species epigenomics, this team aims to better understand the developmental programs underlying bone tumor initiation and progression.

Elucidating the biological mechanisms that lead to bone tumors will allow for the development of better pre-clinical models in which to study the disease and will lead to rational design efforts for developing new drugs for these tumors.

The team of investigators includes: Martin Distel, PhD and Florian Halbritter, PhD of St. Anna Children's Cancer Research Institute, Vienna, Austria; Igor Adameyko, PhD and Matthias Farlik, PhD of Medical University of Vienna, Vienna, Austria; Cornelia Kasper, PhD, University of Natural Resources and Life Sciences, Vienna, Austria

Building on its history as a leading funder in pediatric cancer research, ALSF established the Crazy 8 Initiative to harness collaborative spirit across global institutions to go after the most pressing pediatric cancer research roadblocks. ALSF focused the program to address the eight most challenging aspects of pediatric oncology: embryonal brain cancers; high-grade gliomas; fusion-positive sarcomas; fusion-negative sarcomas; leukemias; neuroblastoma; big data; and catalyzing clinical trials.

While work on the first awarded Crazy 8 Initiative grants is underway, a second Crazy 8 Initiative request for applications was recently issued, bringing the total commitment to $25 million. To learn more visit: https://www.alexslemonade.org/crazy-8-initiative.

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