Anton Henssen: Extrachromosomal DNA in Cancer

Extrachromosomal DNA (ecDNA) as an Engine of Tumor Evolution and Clinical Aggressiveness - and Its Weak Spots

Abstract

Extrachromosomal DNA (ecDNA) has emerged as a major driver of oncogene amplification and therapy resistance in human cancers, but the mechanisms that enable ecDNA to continuously remodel the cancer genome and enhance malignant fitness are only beginning to be defined. Using a combination of single-cell genomics, functional modeling, and patient cohort analyses, our work has revealed that ecDNA is not a static entity: these circular elements can reintegrate into chromosomes, reshaping genomic architecture and accelerating the emergence of aggressive subclones.

We have now identified ecDNA-containing micronuclei as a central, and therapeutically exploitable, node in this process. We find that micronucleus formation silences ecDNA transcription, reduces tumor cell proliferation, and is associated with significantly improved patient outcomes. However, micronuclei can also act as transient reservoirs enabling further ecDNA restructuring, creating a tension between evolutionary innovation and acute fitness cost.

In this talk, I will present published and new data defining how ecDNA reintegration and micronucleus–driven dynamics enable cancer cells to evolve in real time. I will highlight emerging strategies to therapeutically exploit these vulnerabilities. Together, these studies establish ecDNA as a powerful evolutionary catalyst and a clinically actionable hallmark of aggressive disease.

Read more about his research here.

If you can't make it in person, please join via Zoom.