During tumour progression, cells accumulate secondary mutations and/or chromosomal aberrations that generate
genetic diversity within the tumour cell population. This may result in the acquisition of new properties that increase
tumour malignancy, such as invasiveness or resistance to chemotherapy. One of the important mechanisms of chemotherapy
resistance is overexpression or biochemical activation of ABC family transporters. ABC transporters remove antitumour
drugs from the cell, reducing their intracellular concentration and producing resistance against a wide range of
chemically unrelated drugs, known as multidrug resistant phenotype (MDR). During recent decades, much effort has been
devoted to the isolation of compounds able to inhibit the activity of these transporters. However, few such compounds
have reached clinical practice and MDR remains a serious complication in cancer therapy. In an innovative approach to
finding new ABC inhibitors, we propose using fission yeast Schizosaccharomyces pombe as a biosensor of detoxification
that would enable cost-efficient screening of natural compounds and chemical libraries for molecules that revert the MDR
phenotype. Existing fission yeast tools provide genetic, biochemical and cell biological analysis, thereby facilitating identification
of drug targets. Putative inhibitors and modulators of ABC transporters could be used in combination with chemotherapeutic
drugs for the treatment of multidrug resistant tumours.
Keywords: ABC transporter, ABC inhibitor/modulator/chemosensitizer, cancer chemotherapy, drug screen, efflux pump,
multidrug resistance, natural compounds, Schizosaccharomyces pombe.
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