(extrachromosomal DNA in Cancer)


The Challenge

Extrachromosomal DNA

Understanding the biology of ecDNA generation and action, and developing new ways to target these mechanisms in cancer

Team Lead

Paul Mischel Stanford University, US

Countries involved

US, UK, Germany

The Idea

EcDNA doesn’t follow the rules of normal chromosomes, providing tumours a way to evolve and change their genomes to evade treatment. 

We know relatively little about this substantial clinical problem – something the eDyNAmIc team plans to address by bringing new perspectives, unusual collaborations and innovative technologies to the challenge. Using a range of model systems, from yeast to human samples, the team hopes to establish the fundamental mechanisms involved in ecDNA generation, function and maintenance, and its role in tumour evolution and therapy resistance, to identify vulnerabilities that could be exploited for treatment. 

By bridging cutting-edge and diverse approaches and insights from a vast range of fields – yeast genetics, epigenomics, mathematical modelling, evolutionary biology, longitudinal patient tracking, and more – the team hopes to get to the bottom of ecDNA and find ways to drug the undruggable.

Cancer Grand Challenges’ bold, aspirational and interdisciplinary nature has given us an unparalleled opportunity to come together to unlock untapped synergies, hoping to move from incremental to transformational science.