Cancer Drug Resistance: Selection of Resistant Cells

Selection for cancer cells that are resistant to a particular drug: While it is thought that the majority of cancers arise from a single precursor cell, it would be an  error to view a tumor as consisting of a collection of genetically identical cells. One of the hallmarks of cancer is an increase in genetic instability and mutation rates. These changes mean that dividing cancer cells acquire genetic changes (mutations) at a high rate. Practically, this means that the cells in a tumor, while similar, are NOT identical. When exposed to a cancer drug, those cells that are sensitive to the effects of the drug are killed. Those that are resistant will survive and multiply. The result is the re-growth of a tumor that is not sensitive to the original drug. Several reasons for the existence of the initial drug-resistant cells in the original tumor are described over the next few pages. For this reason, and others, chemotherapy drugs are often given in combination. While the likelihood of a particular tumor cell being resistant to several drugs, especially those that attack different cellular processes, is unlikely the large number of cancer cells in a tumor make that a real possibility. The process of cell killing and re-growth of resistant cells is shown in the animation below.⁽¹⁾

1. Gottesman MM. "Mechanisms of cancer drug resistance." Annu Rev Med (2002). 53: 615-27. [PUBMED]