Scientists have discovered a way to target elusive circular fragments of DNA that drive the survival of some of the most aggressive cancers, paving the way for future treatments.

In three papers published today in Nature, scientists from the Cancer Grand Challenges team eDyNAmiC and their international collaborators at the Francis Crick Institute and University College London (UCL) shed light on the unique behaviour of extrachromosomal DNA (ecDNA).

ecDNA are small, circular DNA structures that are common in some of the most difficult to treat cancers.

The papers identify, for the first time, how to specifically target cancer cells containing this malignant DNA, a finding that could make aggressive cancers – such as glioblastoma, triple negative breast cancer or small cell lung cancer – much easier to treat in future.

The research reveals just how commonplace ecDNA is across cancer types and explains how it enables tumours to rapidly alter their genomes to resist treatment.

In one paper, the researchers identified a drug which specifically targets and kills ecDNA-containing cancer cells while sparing normal cells.

A new layer of complexity in cancer evolution

Team eDyNAmiC is funded through Cancer Grand Challenges, a research initiative co-founded by Cancer Research UK and the National Cancer Institute in the US and produced by an international team featuring scientists at Stanford Medicine, the Francis Crick Institute and UCL.

eDyNAmiC team lead and Professor of Pathology at Stanford Medicine, Dr Paul Mischel, said:  “We thought we understood the structure of cancer genomes, but in fact, something very important was missing. The discovery of extrachromosomal DNA, just how common it really is, and what it actually does, reveals a new layer of complexity in cancer evolution. It not only facilitates rapid genetic changes but also highlights the cunning strategies cancer cells use to evade treatment, suppress the immune system, and survive.

“Understanding ecDNA is crucial for developing innovative therapies that can outsmart these relentless adversaries. We hope that these discoveries will yield benefit for patients with the most aggressive forms of cancer.”

Diana Spencer, Senior Digital Content Editor, DDW