Scientists find potential ‘Achilles’ heel’ in oesophageal cancer

Discovery leads to clinical trial in humans with potential for new treatement

Scientists have discovered a new way of attacking oesophageal cancer cells that could make use of an existing drug in a new approach to treatment.

There are 400 cases of oesophageal cancer – one of the most difficult forms of cancer to treat - in Ireland every year.

A team at the Institute of Cancer Research in London have discovered a genetic weakness in oesophageal cancer cells that makes them particularly sensitive to a drug called ibrutinib, which is already used to treat blood cancer.

Their study demonstrated that oesophageal cancer cells with a cancer-causing mutation in a gene called MYC become dependent upon or “addicted” to a second gene, known as BTK.

By blocking the function of BTK using ibrutinib, the researchers were able to kill oesophageal cancer cells grown in the lab, leaving normal cells relatively unaffected. The study is published in the journal Gut.

Attacking “addicted” cancer cells in this way could open up a whole new avenue of treatment for the disease, they suggest. Researchers are now assessing whether ibrutinib will work in oesophageal cancer patients with MYC mutations in a clinical trial at the Royal Marsden Hospital.

Early stage

Irish Cancer Society (ICS) head of research Dr Robert O'Connor said that although this is a relatively early stage laboratory research finding, its publication was welcome, "suggesting as it does a potential new avenue to look for ways to tackle this difficult to treat form of cancer" .

He added: “Each year nearly 400 Irish people are diagnosed with oesophageal cancer (cancer of the pipe which brings food into the stomach), and unfortunately, many patients present late with this disease so treatment can be challenging with only one in five patients (mostly early stage) having durable remission and cure.”

Dr O’Connor added: “We look forward to the results of human trials of the proposed treatment which will tell us in a few years if the new approach proposed is a useful new way of treating this form of cancer.”

Institute of Cancer Research (ICR) professor of cancer genomics Chris Lord said the DNA of cancer cells tended to be "extremely mutated" – while these mutations cause cancer, they also often make cells addicted to genes normal cells are not.

‘Exciting approach’

“Finding which genes cancers are addicted to is an exciting approach for identifying new ways of attacking tumours,” he said. “We can now systematically identify genes which cancer cells need but healthy cells can live without – offering up the potential of precision therapies that have fewer side-effects than conventional treatments.”

Dr Irene Chong, clinician scientist at the ICR and oncologist at the Royal Marsden, said survival rates for patients with oesophageal cancer remain very poor, especially once the disease has started spreading round the body. "We urgently need new treatment options that attack the disease in novel ways."

“Our new study has identified a potential Achilles’ heel in some forms of oesophageal cancer, which we believe could be exploited by new treatments,” she explained. “And because there is an existing drug for other forms of cancer which attacks this weakness, we can test out our new approach rapidly in clinical trials.”

The Irish Cancer Society has urged members of the public to be attentive to the signs and symptoms of cancer and the changes in lifestyle which can reduce the risk of getting it – more details at:

Kevin O'Sullivan

Kevin O'Sullivan

Kevin O'Sullivan is Environment and Science Editor and former editor of The Irish Times