Triple benefit for gene that puts brakes on cancer

A gene that may put the brakes on the development of cancer could form the basis of a test to guide treatment of the disease, scientists report in the British Journal of Cancer¹.

Patients with bowel cancer were three times more likely to benefit from chemotherapy if their tumours tested positive for the gene, according to the study.

Researchers believe that detecting the gene – called SMAD4 – could help doctors to predict whether chemotherapy will work, allowing them to tailor treatments to individual patients’ needs.

The SMAD4 gene seems to rein in cells that are beginning to divide out of control and may protect against bowel cancer. Scientists were interested to see whether it could also affect the success of chemotherapy.

Researchers at the University Hospital of Basel in Switzerland analysed tumour samples from 202 patients with bowel cancer who had been treated with standard chemotherapy, involving the drug 5-fluorouracil.

In healthy bowel tissue, each cell has two copies of the SMAD4 gene. Researchers tested whether the cancer cells in each sample had retained both copies, or whether one or both had been lost. They found that patients whose cancer cells had both copies of the gene were three times more likely to remain free of the disease following chemotherapy than those whose tumours had lost at least one of their copies.

Lead researcher Dr Jean-Louis Boulay comments: “Many people with bowel cancer fail to respond to chemotherapy because their tumours have developed resistance against the treatment.

“Our findings may provide a clue to the genetic basis of the resistance, since tumours with the SMAD4 gene seem more responsive to chemotherapy than those in which the gene is lost.”

In two thirds of patients, at least one copy of SMAD4 was missing from their tumours. These people might not respond well to standard chemotherapy and doctors may need to explore alternative options when looking after them.

Dr Boulay adds: “Testing people for the gene at the time of diagnosis could help doctors to take the right decisions about which treatments to use, improving survival while sparing some patients from drugs which will not do them any good.”

Many drugs used in chemotherapy, including 5-fluorouracil, work by damaging the DNA of cancer cells so badly that they decide to commit suicide. Researchers believe SMAD4 could help cells to take the decision to kill themselves. Without it, cancer cells may decide to plough on despite having damaged DNA, allowing a tumour to grow back after chemotherapy.

Professor Robin Weiss, Editor of the British Journal of Cancer, says: “We know people respond differently to treatment, but at the moment doctors often lack the information they need to treat patients on an individual basis.

“But as we gain a better understanding of how different genes can contribute to cancer’s development and its response to treatment, we’ll be able to plan healthcare for the individual in a much more sophisticated manner than we can now.”

ENDS

1. British Journal of Cancer87 (6)