Federal Grant Award Summary

The University of North Carolina at Chapel Hill received a $388,439 Project Grant from the National Cancer Institute (NCI) under the Cancer Detection and Diagnosis Research program (CFDA 93.394), awarded July 8, 2026, with completion targeted for June 30, 2028. The project delivers two genetically engineered cell reporter platforms designed to detect and monitor the Alternative Lengthening of Telomeres (ALT) pathway, a critical pediatric cancer biomarker. The first platform will detect modulation of C-circles—extrachromosomal DNA circles produced exclusively by ALT-positive cells—in living cells and will be applied to a pooled CRISPR genetic screen to identify key pathway drivers. The second platform will create an ALT-specific reporter system applicable to cultured cells and translatable to model organisms (mouse and zebrafish) to study ALT emergence during normal development and in response to telomerase inhibitor resistance.

These engineered reporter systems address a significant clinical gap: ALT activation drives aggressive pediatric cancers including 65% of osteosarcomas, 25% of high-risk neuroblastomas, 45% of glioblastomas, and 30% of pediatric solid tumors, yet no pathway-specific therapeutic targets currently exist. By enabling real-time monitoring of ALT activity in living cells and providing tools to understand ALT activation mechanisms, the research will facilitate therapeutic discovery and improve understanding of how cancer cells acquire resistance to existing treatments. The deliverables represent proof-of-concept development and validation work in the early-stage technology development category characteristic of NCI's Cancer Detection and Diagnosis Research portfolio.