1. P-glycoprotein (P-gp) is a transmembrane protein involved in ATP-de
pendent efflux of various structurally unrelated anticancer drugs. Its
overexpression in cancer cells decreases intracellular drug concentra
tions and, thus, confers a multidrug resistance phenotype. 2. P-gp is
encoded by MDR genes, which constitute a small gene family comprising
two genes in humans and three genes in rodents. Only the MDR1 gene in
humans and mdr1 and mdr3 genes in rodents have been demonstrated to be
involved in drug resistance. 3. P-gp encoded by the human MDR1 gene i
s a phosphorylated and glycosylated protein 1289 amino acids long, and
consists of 2 halves that share a high degree of similarity. 4. A wid
e variety of cancers have been shown to express P-gp, including solid
tumors and hematological malignancies. This P-gp positivity can be evi
denced at the time of diagnosis prior to chemotherapy or at relapse af
ter treatment, and has been correlated with treatment failure and poor
prognosis in several types of cancer. In addition, P-gp is also expre
ssed by some normal tissues, such as liver and kidney. 5. P-gp express
ion is regulated by various factors, including xenobiotics and hormone
s. 6. P-gp-mediated multidrug resistance can be reversed by various un
related compounds called chemosensitizers or reversing agents. These d
rugs act through inhibition of P-gp function and have entered clinical
trials. Copyright (C) 1996 Elsevier Science Inc.