Drug resistance molecules: lessons from oncology

Abstract

Tumour cell insensitivity to anticancer drugs frequently appears as multidrug resistance (MDR), associated with overexpression of one or more of a set of at least 10 different molecules, causing reduced drug levels at the intracellular target sites. They include transmembrane transporter proteins such as P glycoprotein, MRP1-9 and BCRP. In addition, the lung-resistance protein, recently identified as the major vault protein, has been associated with MDR. We have generated monoclonal antibodies that specifically recognize most of these proteins, which we are using to try to identify their roles in clinical drug resistance, and also to explore their occurrence in normal human tissues and physiology. Both types of studies will also provide further insights into the molecular features of drugs associated with distinct MDR transporters.