Archive for July 28th, 2011
Posted on July 28, 2011, under Cancer.
Cancer cells develop resistance to specific types of drugs in many ways. Perhaps one of the first steps is exposure of the cells to concentrations of drug that are not high enough to kill them. A patient may have been given a dose of chemotherapy that is too low, or a standard dose may have been administered to a patient who has faster metabolism or excretes drugs more rapidly than the average person. Thus, the cells are exposed to low concentrations of drug without being killed. The resulting cancer cells are now “educated” about how to deal with the drug, so that even if the next dose is higher, the cells have a better chance of fending off its toxic effects. That is why chemotherapy drugs must be given in doses that are high enough to kill the cancer cells but below the level that causes severe side effects.
Once cancer cells have been exposed to a specific drug in concentrations that have not killed it, the cells may develop a number of techniques to handle the drug and keep themselves from being killed. Perhaps the most common mechanism that breast cancer cells adopt is the ability to pump the drug outside the cell (55, 56). This action occurs even in normal cells, where it functions to protect the cells from toxins during everyday life (dietary or environmental toxins, for instance).
Cancer cells have other methods of becoming drug resistant. In the case of methotrexate they actually go through elaborate changes in their biochemistry after exposure to the drug. The cancer cells have the ability to increase the amount of protein that is the target for methotrexate—an enzyme called dihydrofolate reductase. With augmented production of the enzyme, the cells have found a way to protect themselves from the lethal effects of the chemotherapy agent.