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Queen’s researchers find key to drug resistant bowel cancer

Queen’s cancer experts have discovered that blocking a molecule could bypass bowel cancer’s defence against the drug cetuximab.

The research, funded by Cancer Research UK, will be presented at the National Cancer Research Institute (NCRI) Cancer conference in Liverpool.

Cetuximab is used to treat advanced bowel cancer, and just under half of bowel cancer patients are given the drug. While it helps many patients, there are some for whom it doesn’t work at all and for others it loses effectiveness.

To understand why this happens, researchers at Queen’s Centre for Cancer Research and Cell Biology treated bowel cancer cells in the lab with cetuximab. They found that some cells survived the treatment by increasing the activity of a protein called ADAM17.

But if they gave a drug that blocked the protein ADAM17 at the same time as cetuximab the cancer cells died.

For other cancer cells, cetuximab treatment alone stopped them growing initially, but over time they became resistant and started growing again. In these cases, the cancer cells were finding a different way to outmanoeuvre the treatment that didn’t involve ADAM17.

Cetuximab is used to treat advanced bowel cancer and works by blocking a molecule known as epidermal growth factor receptor (EGFR), which tells cells to grow.

There are around 41,000 cases of bowel cancer diagnosed in the UK each year. And each year around 16,000 die of the disease.

Dr Sandra Van Schaeybroeck, the lead researcher based at Queen’s, said: “While some bowel cancer patients respond well to cetuximab treatment, many will relapse, or not benefit from the drug. Our work shows that combining this treatment it with an ADAM17 inhibitor could be a promising avenue of therapy for patients who don’t respond to cetuximab by itself.

“More work is needed before we can safely test this combination in patients, but the prospect of cutting off cancer’s path to resistance is very exciting.”

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: "This work shows how some bowel cancer cells are able to avoid damage from a particular drug, and offers a way to prevent it. The next step is to find out whether this could work in patients.

"Bowel cancer is the fourth most common cancer in the UK, and it's the second biggest cancer killer - so it's vital that we find ways to break through the disease's resistance to treatment.”

Professor Richard Wilson, Chair of the NCRI's Colorectal Clinical Studies Group, said: “A big issue facing bowel cancer patients is the prospect of their cancer coming back. This work suggests that further studies are needed to understand all the mechanisms bowel cancer cells are using to evade treatment with cetuximab. By understanding how this happens and how we can stop it will be vital to helping more people survive bowel cancer."


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