Northern Ireland scientists target bowel cancer treatment

Cancer Research N. Ireland scientists are developing a way for doctors to predict which treatment will be most successful in individual bowel cancer patients.

Bowel tumours are often resistant to individual chemotherapy drugs. Giving patients only those drugs that are likely to work would give them their best chance of benefit as well as freeing them of unnecessary side effects.

The team – working under Professor Patrick Johnston at Belfast City Hospital – publish their findings in Clinical Cancer Research1 and plan to use the knowledge to create an exciting new tool in the fight against bowel cancer.

Bowel cancer affects nearly 900 people in Northern Ireland each year and is the Province's second biggest cancer killer.

Knowing how to spot resistance to particular drugs in cancer cells could prove invaluable to doctors when selecting treatments for bowel cancer patients.

For example, the most potent drug against bowel cancer – called 5-FU – is only effective in 40 to 50 per cent of patients, even when used in combination with other drugs.

Identifying patients who are not likely to benefit from treatment with 5-FU drug combinations would enable doctors to pursue other lines of treatment, while freeing patients of the side effects of drugs that are unlikely to help them.

The team generated cancer cells resistant to specific bowel cancer drugs. They then screened the cells to find out what it is about them that makes them resistant to treatment.

Dr John Boyer, who led the project, says: "We have started to create a collection of 'markers' we could look for in cancer cells to tell if they are likely be resistant to certain drugs."

"We believe that identifying such markers is a crucial step towards enabling doctors to give the most appropriate drugs to bowel cancer patients."

Boyer and his team made bowel cancer cells resistant to specific chemotherapy drugs by exposing them to certain drugs in the laboratory over a period of months.

They tested the cells to confirm that they were resistant to the drugs – checking to see whether the drugs could still act on the cancer cells by stopping cell growth or causing the cells to commit suicide.

Finally, they screened the cells for molecules that gave the cells their ability to resist the action of a drug. The molecules hold promise as markers to indicate that a patient's cancer would resist treatment using certain drugs.

The researchers have already identified a number of suitable markers. Cells that are resistant to a widely used chemotherapy drug called oxaliplatin had high levels of a molecule called BCRP.

Finding BCRP in a patient's tumour may therefore prove a useful sign to doctors that oxaliplatin would not be likely to treat that patient successfully.

Team leader Professor Patrick Johnston says: "Ultimately we plan to identify between 50 and 100 markers in bowel cancer cells that will be useful in predicting to which drugs those cells will be resistant.

"We hope doctors will ultimately be able to use these markers to guide them while deciding which drugs to give to their patients."

Professor Robert Souhami, Cancer Research N. Ireland's Director of Clinical and External Affairs, says: "No single chemotherapy drug is suitable for every patient. Finding the drug that will work best should give patients their best chance of survival while allowing them to avoid the side effects of drugs that are not likely to help them."

"Professor Johnston and his team are using an original approach that could help make this a clinical reality."