The Development of Multiple Drug Resistance in Cancer Cells

Abstract

Resistance to chemotherapy, the underlying cause of treatment failure, presents an enormous problem.  40 percent of operable cancers and 80 percent of inoperable cancers are drug-resistant (Vogel).  After the selection for resistance to a single drug, cells can show cross-resistance to other structurally and functionally unrelated drugs.  This phenomenon is called multiple drug resistance.  Through research, it has been found that multiple drug resistance (MDR) is related to ATP-binding cassette transporters, like P-glycoprotein and other related transporters, along with reduced drug uptake and defective apoptotic pathways.  However, each cancer cell in a patient varies in genetic makeup depending on not only the tissue of the organ, but also the pattern of activation of oncogenes, inactivation of tumor suppressors, and random variations in gene expression from the mutated phenotypes of cancers.  Because of these things, every cancer expresses a different array of drug-resistant genes (Gottesman, 2012).