An accidental finding by DCU researchers led to the discovery that certain common drugs can enhance the effectiveness of anti-cancer drugs, writes Dick Ahlstrom.
One of the first examples of Irish basic research being brought straight into Irish clinical medical practice has been recorded by Dublin City University. Curiosity-driven research there has found a way to improve the action of anti-cancer drugs, something now being tested in a patient trial.
Dr Robert O'Connor, a senior research officer at DCU's National Institute for Cellular Biotechnology leads the research team working on the project. Dr John Crown of St Vincent's Hospital Dublin heads the clinical side of the collaboration.
The research relates to the fact that some cancers resist chemotherapy treatments, explains Dr O'Connor. The tumour cells effectively pump out the anti-cancer drugs, so protecting the cell from the damage expected during chemotherapy.
"They are extremely impressive pumps and can pump out large amounts of the anti-cancer drug," he says. Certain tumour types are particularly resistant to treatment as a result of this, he adds, with 40 per cent to 60 per cent of some cancer patients failing to respond to treatment.
Dr O'Connor and his team discovered however that by combining established chemotherapy drugs with certain common drugs used for other purposes, the tumour cell kill rate improved. "We routinely screen anti-cancer drugs in cell cultures to see how they are performing. We also do a lot of work in the drug resistance area as well," says Dr O'Connor. "A few years ago we found by accident that some common non-toxic drugs could increase the potency of certain anti-cancer drugs, inhibiting drug resistance in the cells."
The team combined a commonly used anti-cancer drug, epirubicin, with a non-steroidal anti-inflammatory pain killer, sulindac. Sulindac is harmless to cells, but when linked to epirubicin it increased the potency of the anti-cancer drug by interfering with the tumour cell's ability to pump out the epirubicin.
"We developed a collaboration with Dr John Crown at St Vincent's Hospital and started a Phase I trial with the drug combination," says Dr O'Connor. This was completed about two months ago and the results have yet to be published, but there were surprising findings in relation to some cancer types, he added.
"We found two unusually positive responses with the Phase I group. It wouldn't normally be expected. They showed impressive responses to the treatment," he said.
A Phase I trial is usually about confirming the safety of a new treatment, and the trial included a range of different types of cancer. Two patients in particular, one with lung cancer and another with melanoma, a dangerous form of skin cancer, responded very well to the treatment.
For this reason, Dr O'Connor and Crown will now continue with a new Phase I trial and a Phase II trial, which assesses effectiveness, focusing in particular on breast, lung and melanoma patients.
Dr O'Connor believes this is the first instance of basic research conducted in the State passing all the regulatory hurdles and getting into an Irish-conducted patient trial.
The DCU Educational Trust, the Irish Cancer Society and pharmaceutical giant, Pfizer, funded the research.
Dr O'Connor's work was presented at DCU last Friday during the National Institute for Cellular Biotechnology's first open day. The NICB itself is a Higher Education Authority funded centre under the PRTLI programme.
The NICB also announced a new €34million development project to include a new €10.4million building plus new equipment and staff. The Institute's research programme focuses in particular on the diagnosis and treatment of cancer, microbial infections and diabetes.