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.
Their study discovered a genetic weakness or ‘Achilles’ heel’ in oesophageal cancer cells that makes them particularly sensitive to a drug called ibrutinib which is already used to treat blood cancer.
A team at the Institute of Cancer Research, London, demonstrated that oesophageal cancer cells with a cancer-causing mutation in a gene called MYC become dependent upon or ‘addicted’ to a second gene, 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.
Attacking ‘addicted’ cancer cells in this way, a concept known as synthetic lethality, could open up a whole new avenue of treatment for oesophageal cancer – a disease which affects 9,000 people a year in the UK.
For many patients with oesophageal cancer, the success of existing treatments is limited. The new work is aimed at improving this situation.
The study is published in the journal, Gut, and was funded by Cancer Research UK, the Institute of Cancer Research (ICR), Jansen Ltd., Pharmacyclics Pharmaceuticals, and the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the ICR.
Researchers are now assessing whether ibrutinib will work in oesophageal cancer patients with MYC mutations, in a phase II clinical trial at the Royal Marsden.
By assessing whether patients with MYC-mutated oesophageal cancers respond to ibrutinib, the researchers hope to test whether the laboratory findings translate into an improved way of treating the disease.
To identify this deadly addiction, researchers used a systematic approach, assessing the sensitivity of a large number of oesophageal cancer cells to cancer drugs that are already used in the treatment of other forms of cancer.
In parallel, they also assessed, one by one, the effects of inactivating 720 key genes on cancer cells. By integrating these two approaches, the scientists found the link between BTK addiction and ibrutinib sensitivity in oesophageal cancer cells.