Genetic mechanisms of drug resistance. A review.

An overview of our present understanding of mechanisms of resistance against cytotoxic drugs is presented. Most of this understanding has come from studies on tumor cells made resistant in vitro, but there is reason to think that similar mechanisms are responsible for resistance in patients. After a brief overview of biochemical mechanisms of drug resistance, the types of mutations in tumor cells that can alter drug handling are discussed. Three examples of resistance are analysed in more detail: resistance to the folate analogue methotrexate; the multidrug resistance caused by increased levels of P-glycoprotein, which extrudes drugs from the cell; and resistance to alkylating agents.