Development of drug resistance is a common problem in cancer chemotherapy. For the past several years, investigators have been striving hard to unravel mechanisms of drug resistance in cancer cells. Using different experimental models of cancer, some of the major mechanisms of drug resistance identified in mammalian cells include: (a) Altered transport of the drug [decreased influx of the drug; increased efflux of the drug (role of P-glycoprotein; role of polyglutamation; role of multiple drug resistance associated protein)], (b) Increase in total amount of target enzyme/protein (gene amplification), (c) Alteration in the target enzyme/protein (low affinity enzyme), (d) Elevation of cellular glutathione, (e) Inhibition of drug-induced apoptosis (mutation in p53 tumor suppressor gene; increased expression of bcL-xL gene). Other novel mechanisms in various types of cancer cells include: Over-expression of cytochrome P450 protein, ATP-binding cassette transporter BCRP, sodium channel protein, S-adenosylmethionine synthetase, and loss of functional retinoblastoma protein. An understanding of these mechanisms provides us the basis for the development of drugs which can specifically interact with the cause of resistance and restore the sensitivity of the tumor cell. This reversal of drug resistance has a significant role in modern day cancer chemotherapy.
|Number of pages||10|
|Journal||Pakistan Journal of Medical Sciences|
|Publication status||Published - Apr 2003|
- Cancer cells
- Drug resistance