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Intensify Research on the Major Drivers of Childhood Cancers

NCI has announced several funding opportunities that align with the Cancer Moonshot.

See Funding Opportunities

Chromosomes can rearrange themselves, leading to the formation of fusion oncoproteins. These abnormal fusion proteins are drivers of cancer, particularly childhood cancers. However, there are few cancer therapies that target the type of target fusion oncoproteins that are most common in children. A greater understanding of these fusion oncoproteins is needed to make progress in pediatric cancer research and develop new treatments for childhood cancers.

The goal of this recommendation is to develop a coordinated research effort that will help improve the understanding of these fusion oncoproteins that drive selected cancers. Using a collaborative approach, the network aims to learn more about how fusion oncoprotein-driven cancers develop, create experimental models, identify key dependencies of fusion oncoproteins, and apply this knowledge to create new therapeutic strategies for childhood cancers.

Ultimately, the hope is that the information gained, and progress made from studying these pediatric fusion oncoproteins will provide insight into childhood cancer development and potentially uncover new therapeutic opportunities for pediatric cancers.

NCI has awarded funding to several research projects that align with the panel's recommendation to address the major drivers of childhood cancer, including the:

Fusion Oncoproteins in Childhood Cancers (FusOnC2) Consortium

This collaborative research network is advancing the understanding of the biology of fusion oncoproteins in childhood cancers to inform the development of targeted treatments for pediatric cancer patients. The network brings together researchers with expertise in structural biology, proteomics, genomics, medicinal chemistry, pharmacology, and cancer biology who are teaming up to gain insights into the molecular drivers of childhood cancers.

FusOnC2 is specifically focusing on improving the knowledge of pediatric cancers that are at high-risk for treatment failure, or for which there are currently no known effective targeted therapies. This network is moving the field of childhood fusion oncoproteins forward towards new, more effective treatments with fewer side effects for pediatric cancer patients.

Along with the FusOnC2 network, NCI supports additional interdisciplinary projects to study the mechanisms of action of fusion oncoproteins in childhood cancers. This initiative supports collaborations and was designed to encourage cancer researchers to expand their studies to pediatric cancers. Researchers involved in these projects are investigating molecular events related to pediatric tumor progression, signaling pathways related to treatment resistance in childhood cancers, and the role of the tumor environment in childhood cancers.

Projects Awarded Cancer Moonshot Funding to Address Drivers of Childhood Cancers

Awarded Projects
Funding Opportunity Project Title Institution Principal Investigator(s)
Collaborative Research Network for Fusion Oncoproteins in Childhood Cancers (U54) Targeting SS18-SSX Biology in Synovial Sarcomagenesis University of Utah Jones, Kevin Bruce
The Center for Synovial Sarcoma Biology and Therapeutics Dana-Farber Cancer Institute Kadoch, Cigall; Shilatifard, Ali
An Integrated Approach to Analyze and Target EWS/FLI in Ewing Sarcoma Research Institute Nationwide Children's Hospital Lessnick, Stephen L
The Center for Therapeutic Targeting of EWS-oncoproteins Dana-Farber Cancer Institute

Stegmaier, Kimberly; Armstrong, Scott A

Fusion Oncoproteins in Childhood 
Cancers (FusOnC2) Consortium (U54 Clinical Trial Not Allowed)
Biology and therapy of C11orf95-RELA fusion-driven ependymoma Fred Hutchinson Cancer Research Center Holland, Eric C
Defining and targeting the molecular vulnerabilities of the PAX3-FOXO1 protein in rhabdomyosarcoma Duke University Linardic, Corinne Mary; Counter, Christopher M
Targeting EWSR1-FLI1 through Functional, Structural and Chemical Approaches UT Southwestern Medical Center Mcfadden, David Glenn; Amatruda, James F
Experimental and preclinical modeling of NUP98-rearranged acute leukemia St. Jude Children'S Research Hospital Mullighan, Charles G
Center for therapeutic targeting of the Fusion Oncoprotein of Fibrolamellar Hepatocellular Carcinoma Rockefeller University Simon, Sanford M

Administrative Supplements to Promote Research Collaborations on Fusion Oncoproteins as Drivers of Childhood Cancer (Admin Supp)

The Role of Protein Tyrosine Phosphate PRL3 in Leukemia Development University of Kentucky Blackburn, Jessica S
Biosensor Assay to Screen for Signaling Pathway Inhibition in Cancer University of Minnesota Parker, Laurie L
Imaging Habits in Sarcoma H. Lee Moffitt Cancer Center and Research Institution Martinez, Gary; Gillies, Robert J
A Rapid Spontaneous Murine Model of CN-AML Cincinnati Children’s Hospital Medical Center Grimes, H. Leighton
Aberrant Signaling in Acute Myeloid Leukemia Sloan-Kettering Institute for Cancer Research Kentsis, Alex
Dissecting the Pathogenesis of Ewing Sarcoma with Integrative Genomics Dana-Farber Cancer Institute Stegmaier, Kimberly; Sweet-Cordero, Eric Alejandro
ATP-Dependent Chromatin Remodeling in Human Malignancy Stanford University Crabtree, Gerald R
(PQ5) Investigation of Intertumoral and Intratumoral Heterogeneity of Mitochondrial Apoptotic Sensitivity Dana-Farber Cancer Institute Letai, Anthony G
3D Model of Human Ewing Sarcoma Rice University Mikos, Antonios G; Kasper, Fred Kurtis; Ludwig, Joseph A
Targeting DOT1L for Degradation in MLL-Rearranged Leukemia Dana-Farber Cancer Institute Armstrong, Scott
Pathogenesis and Treatment of NUT-Midline Carcinoma Brigham and Women's Hospital

French, Christopher A.

Research Answers to NCI’s Provocative Questions (R21) Investigating Developmental Hox Programs as Determinants of Sarcomagenesis University of Michigan at Ann Arbor Lawlor, Elizabeth R; Wellik, Deneen M
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