The genetic basis of resistance to cancer chemotherapy.

The Goldie-Coldman hypothesis of how tumours develop resistance to chemotherapy predicts that random mutations occur within a tumour cell population that bestows cytotoxic resistance. These resistance mechanisms may be specific to a certain class of cytotoxic drug, such as changes the enzymes topoisomerase II and dihydrofolate reductase, or may affect many drugs simultaneously, such as increased expression of P-glycoprotein. Knowledge of the genetic basis of these resistance mechanisms will have fundamental clinical importance in individual cases by allowing cytotoxic regimes that are unaffected to be chosen. Moreover, it will allow the development of more effective modulators of resistance.