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Chemotherapy drugs target specific characteristics of cancer cells, which are abnormal cells whose genetic material has mutated. The mutation rate is so high that each tumor is made up of cells with different mutations. These can allow the cell and its products to change appearance. The anticancer drug may not recognize the target cells, or the tumor can actively block the drug from doing its job. Mutations and their results are therefore very important for research into drug resistance in cancer.
Drug resistance in cancer develops when the tumor contains both susceptible and resistant cells. The drug kills the susceptible cells but leaves the resistant ones. Initially, the drug can shrink the tumor and the treatment appears to be working.
As a characteristic of cancer cells is that they proliferate uncontrollably, the remnants of the cancer can begin to grow again. Chemotherapy therefore commonly uses more than one drug. The different actions of the drugs can target cells with various mutations.
Every time a cell reproduces, the genetic material inside the cell can suffer from mutation, which is a change in the genetic sequence. The genes of a cell are the blueprint for the structure and the products of that cell. Mutations can be beneficial, neutral, or detrimental to the cell. Beneficial mutations sometimes allow the cell to survive attack, and this results in drug resistance in cancer.
Occasionally, cancer cells can contain an abnormal amount of chromosomes. Humans usually have 46 chromosomes, of which half are duplicates of the other 23. Drug resistance in cancer is more likely if the tumor contains cells with less or more than 46 chromosomes.
Anticancer drugs may have to enter the cell to perform the therapeutic action. The outside structural components of the cell can be altered through a genetic mutation. These components can be altered or the numbers of targets for the drugs may be reduced.
In the case of the estrogen receptor in breast or ovarian cancers, the target component may be lost altogether. In these cases, the drug cannot get through the membrane in adequate amounts or at all. Tumor cells may also be able to send the drug back out of the cell after it gets in. The cancer cell may also have an increased ability to break down the drug once inside.
Another drug may work by binding to a particular molecule and blocking its function. If the gene for the target is mutated, the appearance of the molecule can change enough to avoid detection by the drug. The cell may also produce an increased concentration of the target molecule, allowing some to escape the drug. This can happen if the cell's genome contains more copies of the relevant gene than usual or if the cell can stimulate the gene to produce many more molecules than usual.
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