Why isn't my chemotherapy working?
My doctor tells me my chemotherapy isn't working any more and my cancer is growing. Why is this?
Your cancer seems to have become resistant to the chemotherapy you have been having. This can happen to some people, unfortunately. Cancers develop from normal cells that have changed or mutated to become cancerous. The mutation happens in the genes of the cell. These changes make the cell behave differently to a normal cell. Cancer cells continue to mutate, so that they become more and more abnormal. Sometimes the mutations make the cells resistant to chemotherapy.
Your doctor may want to try some different chemotherapy. But unfortunately, sometimes cancers develop resistance to many chemotherapy drugs at the same time. Doctors call this multidrug resistance. Scientists have found a group of genetic mutations that they think cause this. These mutations mean that the cancer cell can keep the drugs out. The resistant cells have high levels of a substance called p-glycoprotein. P-glycoprotein is a protein found in cell walls. The protein acts as a pump and removes toxins from cells. Cells with high p-glycoprotein levels are very good at keeping chemotherapy drugs out. If there is not enough of a chemotherapy drug inside a cancer cell, the drug cannot kill the cell.
Researchers have been working on this problem almost as long as chemotherapy has been used. If we are to make chemotherapy treatment more effective for more types of cancer we need to find a way of overcoming resistance.
Cancer Research UK researchers have now developed a way of blocking p-glycoprotein. They are working on a drug called tariquidar (XR9576). Tarquidar blocks (inhibits) p-glycoprotein. Doctors have known tariquidar could work in individual cells for some time. The drug has shown some effectiveness when given to patients as part of early phase 1 and 2 trials but it caused a lot of side effects. Further trials are being carried out mainly in America to try to find out exactly how effective tariquidar is, and to reduce the side effects. A recent trial looked at giving tariquidar and paclitaxel together in a fat capsule (liposome). Putting tariquidar in the fat capsules reduces the side effects as there is less exposure of normal tissues to the drug. The trial results are promising.
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