with ecDNA. Scientists could see all sorts of strange, unaccountable things happening – tumours spreading with unanticipated speed or cancers becoming resistant to drugs that had initially been effective in attacking them. “Now, at last, we have revealed the agents of these events. It is ecDNA,” added Chang.
The breakthrough is part of a major initiative, known as the Cancer Grand Challenges, that is backed by Cancer Research UK and the US National Cancer Institute. It has been set up to fund multidisciplinary research programmes that could develop novel routes for tackling cancer. In this case, it has provided £20m to fund the work on ecDNA’s involvement in cancers and has involved teams of chemists, biologists, geneticists, mathematicians, and immunologists – based in California, London and other centres – collaborating to show how these little loops of DNA cause such biological harm.
In recent years, scientists have shown that tumours occur because normal genes in a cell go wrong and cause that cell to divide uncontrollably. The end result is a tumour. These genes are known as oncogenes and they can be targeted by a range of drugs and therapies.
“However, resistance to those drugs or therapies often appears after a while, and this allows the cancer to return. We have now discovered that, in some of the most aggressive forms of cancer, the oncogenes aren’t where we thought they were. They are actually on extrachromosomal DNA,” said Mischel.“The vulnerable gene had quickly disappeared when threatened by cancer drugs and was hidden in ecDNA. Then it reappeared once it was safe for it to start causing damage again.”
From this perspective, ecDNA is not just a villain. It is a criminal mastermind. “It can almost completely disappear from a tumour and then come back after you stop drug treatments,” said Professor Charlie Swanton of the Francis Crick Institute in London. “That provides almost infinit