P-glycoprotein and resistance to anticancer drugs

✍ Scribed by Victor Ling

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 661 KB
• Volume: 69
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19920515)69:10<2603::aid-cncr2820691034>3.0.co;2-e

✦ Synopsis

Advances in chemotherapeutic treatment of human cancers will depend on our acquiring a real understanding of what factors limit successful therapy. One factor postulated to be important is the acquisition of a drug resistance phenotype by the patient's malignant cells. Particularly, it is thought that tumor cells acquiring simultaneous resistance to a diverse group of drugs, the so-called multidrug resistance (MDR) phenotype, are the most insidious. It is now clear that a major mechanism of MDR in mammalian cells involves an increased expression of a 170-kDa plasma membrane glycoprotein, P-glycoprotein. The broad concept that P-glycoprotein functions as an energy-dependent drug efflux pump with a surprisingly broad specificity has now been firmly established. However, details of how such a biological pump functions remains enigmatic. Nevertheless, it is increasingly apparent that the P-glycoprotein mechanism of MDR has clinical significance, and the prospect of exploiting fundamental knowledge of this protein for improving therapeutic efficacy of some nonresponsive cancers appears bright.

In recent years, numerous reviews documenting progress made in the molecular biology, biochemistry, pharmacology, and clinical relevance of P-glycoprotein and MDR tumor cells have been published.'-7 I offer here a brief personal perspective on some of the re-~~