HMN 2026: why some esophageal cancers are so hard to treat

New research has uncovered new insights into why the most aggressive esophageal cancers are so difficult to treat and how the body’s own defense systems are helping them to thrive. The study, led by Professor Eileen Parkes and her team in the Department of Oncology at the University of Oxford and published in Science Advances, analyzed patient-donated tumor samples and found that the most dangerous types of esophageal 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 tumor interacts with the body’s own defense systems.

Using newly developed laboratory models of esophageal cancer, the researchers found that cancers with unstable chromosomes “switch on” certain genes. These genes were shown to send out chemical signals that attract inflammatory immune cells into the tumor, bolstering its defense.

“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 esophageal cancer in a way that actually helps the tumor,” said Dr. Bruno Beernaert, postdoctoral researcher in the Parkes lab and DPhil in Cancer Science alumnus. “Instead of triggering an effective immune attack against itself, the cancer appears to hijack the body’s own defense 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 esophageal cancers are particularly resistant to existing therapies and point to new potential treatment strategies.

“By uncovering how chromosomal instability reshapes the tumor’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.”

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