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
|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|