New Research Reveals Why Some Oesophageal Cancers are So Hard to Treat

 The study, led by Professor Eileen Parkes and her team in the Department of Oncology at the University of Oxford, analysed patient-donated tumour samples and found that the most dangerous types of oesophageal cancers share a key feature: high chromosomal instability. This means the cancer cells constantly make mistakes as they grow and divide, making them more aggressive, harder to treat, and allowing them to adapt more easily.

However, the research team discovered that this instability doesn’t just make the cancer grow faster: it also changes how the tumour interacts with the body’s own defence systems.

Using newly developed laboratory models of oesophageal cancer, the researchers found that cancers with unstable chromosomes ‘switch on’ certain genes. These genes were shown to send out chemical signals that attracted inflammatory immune cells into the tumour, bolstering its defence.

“We’ve known for some time that chromosomal instability makes cancer more aggressive, but what we’ve discovered is that it also fuels inflammation in oesophageal cancer in a way that actually helps the tumour,” said Dr Bruno Beernaert, postdoctoral researcher in the Parkes lab. “Instead of triggering an effective immune attack against itself, the cancer appears to hijack the body’s own defence systems, the immune response, to help it to survive treatment and spread.”

The findings may help to explain why some of the most aggressive types of oesophageal cancers are particularly resistant to existing therapies and point to new potential treatment strategies.

“By uncovering how chromosomal instability reshapes the tumour’s immune environment, we’ve identified a potential vulnerability,” added Professor Parkes. “If we can disrupt this inflammation pathway, we may be able to suggest new treatment options which improve outcomes for patients.”

Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS–chemokine–myeloid axis is published in Science Advances.

^{This work was part-funded by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre.}

^{Aspects of this research were carried out as part of Dr Beernaert’s DPhil in Cancer Science at the University of Oxford. DPhil in Cancer Science Students are supported by a grant from Cancer Research UK, managed through the CRUK Oxford Centre.}

^{Professor Parkes is directly supported by the Wellcome Trust via a Clinical Research Career Development Fellowship.}