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What Is Chemotherapy Resistance?

By Jillian O Keeffe
Updated May 17, 2024
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When a tumor is resistant to a drug, the drug has little or no effect on the cancer. Chemotherapy resistance occurs when the tumor changes slightly to become less vulnerable to a drug whereas before the drug regimen was able to control or even shrink the tumor. Tumors, by their very nature, are cells that grow out of control. This constant growth is the way resistance mechanisms can evolve, as some cells are killed by the drug, but some newly mutated ones survive and prosper.

Tumors are collections of cells that have genetic damage that causes them to grow uncontrollably. A successful chemotherapy drug targets the tumor cells and does no significant damage to the other, healthy cells of the body. Problems in treatment may arise when the tumor cells that previously in the treatment regimen were dying off from the drug, become immune to the drug. This process is called chemotherapy resistance, and is a cause for concern for both patients and doctors.

Every cell, whether it is a normal or a cancer cell, has cell machinery. The structure of the cell contains transporter molecules, which carry in certain molecules and expel others. Each tumor is a collection of cells, which can be present in a solid lump, or as a scattering of cells. All of the cancer cells in a patient are not entirely identical, and all of the genes in each cell do not express to the same extent, and it is these difference that can allow chemotherapy resistance to develop.

For example, while all the cells have a gene that tells the cell to make a particular protein, only some of the cells have a gene that is more active than normal. This tells the cell to make plenty of the protein. If this protein is a molecule that pushes out certain substances like the chemotherapy drug from the cell, then this cell is more resistant to the drug. Conversely, if the tumor cell produces less of a protein that pulls in the chemotherapy drug, then this cell will also have more resistance to the drug.

Cells that produce abnormal versions of the transporter molecule then this cell may also be less vulnerable to the drug. Abnormal versions of other substances in the cell, such as regulatory molecules, which control certain reactions, can also confer resistance to the cell, if they reduce the amount of drug getting into the cell, or increase the amount of drug that the tumor can push out of the cell. Genetic features of resistant tumor cells can also include a higher than normal ability to fix cellular damage caused by chemotherapy.

Chemotherapy resistance occurs because a tumor has some variations in its individual cells. At the beginning of treatment, the anticancer drug may kill off most of the tumor cells, but the cells that already, accidentally, contain these abnormal but beneficial features, survive. With time, these cells grow, and a new drug is required to destroy the cells. Some resistance mechanisms may also be able to give the cells resistance to more than one type of drug.

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