Irish scientists could make important improvement in cancer treatment

Many cancers, especially lung, colon and breast, either are resistant to chemotherapy or after initially responding, become resistant to a wide range of the most active chemotherapeutic drugs, making it increasingly difficult to treat and cure the patient.

Sometimes this resistance is caused by high levels of a protein called MRP-1 (multi-drug resistant associated protein) that sits on the surface of the cell and prevents access to the cancer by pumping the drug back out of the cell. The normal purpose of these pumps is to prevent toxins or chemicals from invading healthy cells. The pumps recognise the chemotherapy drugs as powerful toxins and go to work to repel them.

Now, scientists at the National Institute for Cellular Biotechnology at Dublin City University have discovered that a number of commonly-used painkillers from a family of drugs knows as NSAIDs (non-steroidal anti-inflammatory agents) block the action of this pump and make resistant cancer cells become sensitive to anti-cancer drugs once again.

"We have been studying the mechanics of the MRP-1 protein in order to identify the drugs that will block its pumping mechanism." Explained Professor Martin Clynes, director of the NICB at DCU.

Professor Clynes and his team, working with pathologist Dr Susan Kennedy and surgeons Mr Vincent Lynch, Mr Arnold Hill and Mr Enda McDermott at St Vincent's Hospital, examine tissue biopsies from patients before they receive chemotherapy and compare the levels of MRP-1 from patients who are cured with those who subsequently relapse. Under laboratory conditions, they also grow cancer cells, make them resistant to anticancer drugs and study the activity of the protein pump. Their research shows that when specific painkiller drugs are introduced into the cells, the chemotherapy begins to work again.

"We hope that the combination of particular painkillers with chemotherapy treatment will be more effective than chemotherapy alone because the painkillers break down the cancer cells' resistance to the chemotherapy." Said Dr Robert O'Connor of the NICB.

The research has now reached clinical trial, phase one and has been approved by the Irish Medicines Board. This research stage is being carried out by Dr John Crown and Dr Michael O'Leary at St Vincent's Hospital in Dublin and involves testing various drug combinations on human cancer patients. It may take up to two years before researchers are ready to move to phase two clinical trial. At this point the drug combinations will be tested on a much larger number of patients.

The research has been funded by the DCU Educational Trust, the Health Research Board and the Irish Cancer Society.

This research is unusual in Ireland as it takes a new cancer treatment all the way from basic discovery through development and into clinical trials. If successful, the treatment can be used throughout the world and could save the lives of many more cancer sufferers.

Ends.