Type

Journal Article

Authors

Robert O'Connor

Subjects

Pharmacology

Topics
animals drug resistance neoplasm atp binding cassette transporters neoplasms pharmacokinetics antineoplastic agents humans metabolism drug therapy pharmacology

The pharmacology of cancer resistance. (2007)

Abstract 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.
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Full list of authors on original publication

Robert O'Connor

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Robert O'Connor
Dublin City University
Total Publications: 74