P-glycoprotein (Pgp), the product of the human MDR1 gene responsible for a major form of multidrug resistance in tumor cells, is a transmembrane protein that carries out ATP-dependent efflux of various lipophilic compounds, including many anticancer drugs. Pgp renders tumor cells resistant to such drugs, and Pgp expression has been shown to correlate with clinical drug resistance or negative prognosis in several types of cancer.
The best known form of multidrug resistance in mammalian cells involves cross-resistance to a large group of lipophilic drugs with different structures and mechanisms of action. Cellular targets of such drugs include microtubules (vinblastine, vincristine, Taxol, colchicine), topoisomerase II (doxorubicin, etoposide), RNA polymerase (actinomycin D), ribosomes (puromycin), plasma membrane (gramicidin D), and mitochondria (rhodamine 6G). This multidrug resistant phenotype is due to...