Chemotherapy is frequently used to kill cancers but some tumours can develop a resistance to these drug treatments. The cancer cells are able to pump the toxic chemicals out, allowing them to survive and grow.
A research team at the National Cell and Tissue Culture Centre at Dublin City University may have found a safe and simple way to prevent drug resistance in at least some of these cancers.
Organisms have developed a wide range of strategies to protect themselves against toxic materials, explained Prof Martin Clynes, director of the centre, which is one of the five university-based BioResearch Ireland labs. During evolution, animals developed pumps to protect individual cells from environmental poisons and other toxins.
These cell pumps are actually proteins manufactured inside the cell which, when produced, entwine themselves into the cell's outer skin or membrane. These pumps are poorly understood and there are several models for how they work. They use energy so it is an active process, but how they manage to push toxins out of the cell has yet to be fully explained.
"Some cancers produce these [pump] proteins in very large amounts," Prof Clynes said. "This makes them very efficient at clearing out the powerful toxins given during chemotherapy."
Cancer cells grow and divide much more quickly than ordinary tissues. Chemotherapy involves giving the patient a cell poison which does more damage to rapidly dividing cancer cells than to normal cells. Some cancers survive this treatment better than others, however, and some of these manage this by producing excess pump proteins.
Prof Clynes's group has focused on one of the three main pump proteins, MRP (multi-drug resistant associated protein). "It does look like a number of human cancers overexpress MRP," he said. His group has discovered, however, that the action of the MRP pump can be blocked by certain painkilling drugs, several of the non-steroidal anti-inflammatory drugs which are in widespread use. "We are not certain about their mechanism but we know that they bind to the pump and stop it working," he said.
The theory would follow that if the tumour cell's ability to pump out the chemotherapy drugs was inhibited, then more cancer cells would be killed off. This in fact has been shown in several tests done by the DCU lab. The team initially tested this in tissue cultures and the cancer cell kill rate improved when chemotherapy drugs and an anti-inflammatory were given together.
Mice with tumours were then tested and the combination was again found to work better than traditional chemotherapy alone. Special mice carrying human tumours were next tested and better results were seen with the combination. "We had a better effect with the anti-cancer drugs with the painkiller than when using the anticancer drug alone," Prof Clynes said.
He pointed out that the work is an "indicator" and not a new wonder cure. The combination has not been tested in human trials and much work would be needed to work out a safe treatment regime. It would also only have application in a proportion of drug-resistant cancers, those where MRP was over-expressed.
The group has sought a patent however and is now trying to attract pharmaceutical company interest so that trials can be conducted. It represents yet another small but significant step in the fight against this disease, Prof Clynes believes.