Cancer Drug Resistance: Changes in Target Molecules
The target molecule is no longer present: It is possible that the target of a particular treatment is lost during the progression of cancer development. An example would be the loss of the estrogen receptor (ER) from breast or ovarian cancer cells. This change would theoretically render the use of the anti-estrogen drug tamoxifen much less effective. The loss of the ER from these cells is an indication that the cells are no longer dependent on the presence of estrogen as a growth stimulator. For this reason, the status of the ER is often determined during the initial phase of breast and ovarian cancer diagnosis.(1)
The target molecule is altered: Gene mutation is common in cancer cells. Exposure to chemotherapy drugs can kill cells that have a normal version of a particular target while sparing those that have acquired a modifed version of the gene. While the slightly altered version of the gene may still function in the cell, it can no longer be inhibited by that particular drug. The process is depicted below.(1)
An example of the above process is the selection for drug resistance in patients treated with the kinase inhibitor Gleevec®. Recent research has identified specific mutations in the target gene that render the protein resistant to the drug.(2)
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