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Drug Resistance in Cancer Cells

by Susan E. Bates Zahid H. Siddik Kapil Mehta

The inability of cancer drugs to destroy metastatic tumors is the major reason why cancer therapy fails. Even though the process of drug design has become exceedingly sophisticated in recent years, there is not a single drug available that is 100% effective against metastatic cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic/genetic differences in tumors, even those from tissue of origin. Although it is a generally accepted fact that the majority of cancers arise from a single precursor cell, it is naïve to consider that tumor is a collection of genetically identical cells. Genetic instability and accumulation of mutations are important hallmarks of cancer cells. This means that dividing cancer cells are able to acquire genetic and epigenetic changes that will favor their malignant phenotype. In view of this, it is fair to say that the cells in a given tumor may be similar but not identical. Therefore, when treated with a drug, the sensitive cells in a tumor succumb to the toxic effects of the drug, and resistant cells continue to survive and multiply. The tumor, which re-grows from these residual resistant cells, is not sensitive to the original drug.

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