Team eDyNAmiC has made important new mechanistic and clinical discoveries, as well as developed new enabling tools. As Year 4 of our award ends, we are eager to continue the momentum as we enter Year 5. Below, we present 10 areas of high impact.
1. We identified DNA retention elements that ecDNAs use to tether to chromosomes during cell division and showed that they are required for ecDNA maintenance.
2. We discovered that ecDNAs are a platform for oncogene transcript fusions, revealing a prevalent landscape of oncogene fusions dictated by tissue site, enhancing tumorigenicity.
3. We found that ecDNAs can activate enhancers through amplification of transposable elements.
4. We gained additional new insight into how ecDNA suppresses the cGAS-STING pathway, and how its chemical reactivation can dramatically inhibit the growth of ecDNA containing tumours.
5. We learned how ecDNA drives rapid adaptation to therapy for children with NMYC-amplified neuroblastomas and conducted extensive spatial analyses and modelling to reveal a multi-step model of glioblastoma pathogenesis through ecDNA.
6. We developed new technologies for detection and analysis of ecDNA, including new technologies for detection of ecDNA from single cell datasets.
7. We completed the TRACERx/PEACE multi-region, longitudinal, whole genome sequencing (WGS) cohort for ecDNA analysis and established a pilot long-read plasma sequencing workflow within TRACERx for plasma ecDNA detection.
8. We developed a new tool for resolving the 3-dimensional structure of ecDNA molecules, developed new ecDNA mouse models, and advanced our chemical biology efforts, including structural analysis of covalent ligands targeting ecDNA proteins of interest and identifying first-in-class ligands for several ecDNA proteins.
9. Team eDyNAmiC published 18 papers and 4 reviews in year 4, including studies in Nature, Cell, Nature Cell Biology, Cell Chemical Biology, and Cancer Discovery.
10. We achieved one of our key goals this year, working very closely with the DepMap team to include ecDNA filters into the next DepMap update.
During year 4: i) Team eDyNAmiC’s work was highlighted in a feature article in Science Magazine and in the “Clinical Implications of Basic Research” section of the New England Journal of Medicine; ii) the inaugural CGC Conferences devoted to ecDNA was held in June of 2025; iii) in July 2025 Team eDyNAmiC received the Cancer Research Horizons Explorer Recognition Award celebrating the team’s groundbreaking research to redefine our understanding of ecDNA in cancer; iv) ecDNA selected for an opening plenary talk and major symposium at AACR 2025 and for a major Symposium in 2026; v) ecDNA has now become recognized as one of the “hottest” and most important areas of cancer research. Since the Cancer Grand Challenges Award, 410 ecDNA papers have been published, with the CGC program acting as a global scientific amplifier. Team eDyNAmiC collaborates widely, sharing tools, models, data, and expertise to support new investigators and expand the field.
