Cisplatin - 17. Drug Resistance Cisplatin 17. Resistance occurs when cells once destroyed by a particular drug no longer respond to treatment with that drug. Indeed, drug resistance has significant clinical implications.
Drug resistance can operate by a number of mechanisms, none of which is fully understood.
Postulated mechanisms of cisplatin drug resistance include decreased intracellular accumulation of cisplatin, increased intracellular levels of certain sulfur-containing macromolecules, and increased DNA repair. If cisplatin cannot accumulate in the cell, it cannot reach the DNA found inside the cell, bind the DNA, and cause cell death. The mechanism of decreased intracellular accumulation of cisplatin is not well understood, but it appears that the cell has some control over whether cisplatin enters the cell. This suggests that cisplatin does not enter the cell by passive diffusion alone but that there is some active transport system involved. Furthermore, additional experiments have shown that decreased cellular accumulation of cisplatin is not due to increased efflux of cisplatin.