RT Journal Article
SR Electronic
T1 The Pharmacology of Cancer Resistance
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1267
OP 1272
VO 27
IS 3A
A1 O'CONNOR, ROBERT
YR 2007
UL http://ar.iiarjournals.org/content/27/3A/1267.abstract
AB Many tumour cells become resistant to commonly used cytotoxic drugs due to the overexpression of ATP-binding cassette (ABC) transporters. Two proteins, P-gp (MDR-1, ABCB1) and MRP-1 (ABCC1) have been demonstrated to pump a wide selection of the most commonly used cancer drugs and their overexpression correlates broadly with negative treatment response characteristics in many different forms of cancer. Several generations of pharmaceutical inhibitors of P-gp have been examined in preclinical and clinical studies; however, these circumvention trials have largely failed to demonstrate the anticipated increase in therapeutic efficacy. In vitro screening has identified a number of pharmaceuticals which can selectively inhibit pumps such as P-gp, or MRP-1, by virtue of their being substrates for these pumps. The use of low toxicity pharmaceuticals or agents which have anticancer properties as ABC transporter inhibitors may allow a new paradigm of clinically useful drug resistance circumvention. Our increasing understanding of the complex pharmacological interplay of drug transporter proteins indicates that the cellular pharmacokinetics of cancer drug entry into and exit from tumour cells is of prime importance in subsequent drug efficacy and a larger portfolio of pump modulators and targeted efflux inhibition strategies is necessary to effectively overcome multiple drug resistance. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved