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Targeting Fusion Oncoproteins in Childhood Cancers (TFCC)

Generation of Fusion Proteins Through Chromosomal Rearrangement Enlarge

Fusion proteins, which can occur when parts of different chromosomal regions are joined, may drive the development of many cancers in children.

Credit: Shannon McArdel, Ph.D. Harvard University SITN Blog, June 2017. CC BY-NC-SA 4.0.

The overall goal of the Targeting Fusion Oncoproteins in Childhood Cancers (TFCC) Network is to form a dynamic and collaborative team of investigators to advance our understanding of the mechanisms of action of fusion oncoproteins in pediatric cancers and apply novel chemical strategies to accelerate innovative drug discovery and preclinical development of therapeutics for fusion oncoprotein-driven childhood cancers. 

The TFCC network, funded by DCB and the NCI Division of Cancer Treatment and Diagnosis (DCTD), includes:

  • Researchers investigating the molecular mechanisms by which fusion oncoproteins drive childhood cancers.
  • Multidisciplinary research groups working at Next Generation Chemistry Centers that are focusing on innovative medicinal chemistry, chemical biology and chemoproteomic approaches to target fusion oncoprotein-driven cancers. 

This program aims to combine therapeutic approaches with continued mechanistic studies to reveal potential treatment targets and advance the development of therapeutic strategies for fusion oncoprotein-driven childhood cancers.  

Impact of Fusion Oncoprotein Research

Progress in our understanding of fusion oncoprotein-driven cancer biology through investigator-initiated research and the Cancer Moonshot-funded Fusion Oncoproteins in Childhood Cancers (FusOnC2) Consortium, along with recent technological developments, provides an opportunity for collaborative efforts towards the development of new treatment approaches for childhood cancers.  

Advances in chemical biology have expanded the universe of “druggable” protein targets in pediatric cancers and new technological approaches provide strategies for the direct targeting of fusion oncoproteins and the proteins with which they interact within complexes. Progress in medicinal chemistry (such as PROTACs and molecular glues) provides a knowledge base for the design of new therapies for fusion-driven childhood cancers. 

While directly targeting fusion oncoproteins would be ideal because of their exclusivity in tumors, other targets (e.g., interacting proteins, synthetic lethal partners, mediators of fusion oncoprotein function) may be more amenable to these strategies. 

The TFCC aims to build on the progress of fusion oncoprotein research and translate preclinical discoveries into the development of effective treatments for fusion oncoprotein-driven childhood cancers.

TFCC Funding Opportunities

  • RFA-CA-23-036: Mechanisms of Fusion-Driven Oncogenesis in Childhood Cancers (U01 Clinical Trial Not Allowed)
  • RFA-CA-23-037: Next Generation Chemistry Centers for Fusion Oncoproteins (UM1 Clinical Trial Not Allowed)

TFCC Pre-Application Webinar Materials

On Aug. 11, 2023, NCI staff held a pre-application webinar about the TFCC funding opportunities. 

Contacts for TFCC  

For additional information about TFCC, please contact Dr. Keren Witkin in DCB or Dr. Joseph Agyin in DCTD. 

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