Antineoplastic resistance
Antineoplastic resistance is the multidrug resistance of neoplastic (cancerous) cells, rather than drug resistance involving microorganisms such as bacteria, fungi and viruses. Cancer cells have the ability to become resistant to multiple drugs by many mechanisms:[1]
- Increased efflux of drug (as by P-glycoprotein (ABCB1), multidrug resistance-associated protein (ABCC1), and breast cancer resistance protein (also known as mitoxantrone resistance associated protein, MXR, or ABCG2)
- Enzymatic deactivation (i.e., glutathione conjugation)
- Decreased permeability (drugs cannot enter the cell)
- Altered binding-sites
- Alternate metabolic pathways (the cancer compensates for the effect of the drug).
Because efflux is a significant contributor for multidrug resistance in cancer cells, research has been aimed at blocking specific efflux mechanisms.[2] Treatment of cancer is complicated by the fact that there is a variety of different DNA mutations that cause or contribute to tumor formation, as well as myriad mechanisms by which cells resist drugs.
Notable differences between antibiotic drugs and antineoplastic (anticancer) drugs that complicate their design are that cancer cells are altered human cells and thus more difficult to damage without damaging healthy cells.
See also
References
- ↑ Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. http://www.cancerci.com/content/15/1/71
- ↑ Modok S, Mellor HR, Callaghan R (August 2006). "Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer". Curr Opin Pharmacol 6 (4): 350–4. doi:10.1016/j.coph.2006.01.009. PMID 16690355.
Further reading
- Guminski AD, Harnett PR, deFazio A (May 2002). "Scientists and clinicians test their metal-back to the future with platinum compounds". Lancet Oncol. 3 (5): 312–8. doi:10.1016/S1470-2045(02)00733-7. PMID 12067809.
- Krishan A (2001). "Monitoring of cellular resistance to cancer chemotherapy: drug retention and efflux". Methods Cell Biol. 64: 193–209. doi:10.1016/s0091-679x(01)64014-7. PMID 11070840.
External links
- CancerDR: Cancer Drug Resistance Database. Scientific Reports 3, 1445