[gdpawel]

Drug resistance is a major problem with conventional cytotoxic chemotherapy agents. This is because most cancer cells are genetically unstable, are more prone to mutations and are therefore likely to produce drug resistant cells. However, since angiogenic drugs target normal endothelial cells which are not genetically unstable, drug resistance may not develop. So far, resistance has not been a major problem in long-term animal studies or in clinical trials, and neither has it with assay-directed therapy.

Even in previously failed therapies, results from phenotype analysis have seen numerous occasions in which a drug used years earlier becomes effective again, once the tumor has been removed from the selective pressure of drug exposure. The tumor loses the capacity to resist. One can test almost any drug in the laboratory, providing the whole "live" tumor is available. Changes induced by subsequent treatment may bring the tumor back to a point where failed drugs are viable again. A number of these laboratories have tested many small molecules and in the past studied the P-glycoprotein and GST inhibitors to reverse drug resistance.