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Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets

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Multi-Drug Resistance in Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 596))

Abstract

Resistance of tumor cells to several structurally unrelated classes of natural products, including anthracyclines, taxanes, and epipodophyllotoxines, is often referred as multidrug resistance (MDR). This is associated with ATP-binding cassette transporters, which function as drug efflux pumps such as P-glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1). Because of the hypothesis in the early eighties that blockade of these efflux pumps by modulators would improve the effect of chemotherapy, extensive effort has been put to visualize these pumps using nuclear imaging with several specific tracers, using both SPECT and PET techniques. The methods and possibilities to visualize these pumps in both the tumor and the blood–brain barrier will be discussed. Because of the fact that the addition of Pgp or MRP modulators has not shown any clinical benefit in patient outcome, these specific MDR tracers are not routinely used in clinical practice. Evidence emerges that combination of chemotherapeutic drugs involved in MDR with the so-called targeted agents can improve patient outcome. The concept of molecular imaging can also be used to visualize the targets for these agents, such as HER2/neu and angiogenic factors such as vascular endothelial growth factor (VEGF). Potentially visualizing molecular drug targets in the tumor can function as biomarkers to support treatment decision for the individual patient.

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Acknowledgments

Supported by a personal grant (W.B. Nagengast) and grant RUG 2007-3739 of the Dutch Cancer Society.

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Authors and Affiliations

  1. Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands

    Wouter B. Nagengast, Thijs H. Oude Munnink, Eli C. F. Dijkers, Geke A. P. Hospers, Adrienne H. Brouwers, Carolien P. Schröder, Marjolijn Lub-de Hooge & Elisabeth G. E. de Vries

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  1. Wouter B. Nagengast
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  2. Thijs H. Oude Munnink
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  3. Eli C. F. Dijkers
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  5. Adrienne H. Brouwers
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  6. Carolien P. Schröder
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  7. Marjolijn Lub-de Hooge
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  8. Elisabeth G. E. de Vries
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Correspondence to Elisabeth G. E. de Vries .

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  1. College of Life Sciences, Nankai University, Weijin Rd. 94, Tianjin, 300071, China, People's Republic

    Jun Zhou

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Nagengast, W.B. et al. (2010). Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets. In: Zhou, J. (eds) Multi-Drug Resistance in Cancer. Methods in Molecular Biology, vol 596. Humana Press. https://doi.org/10.1007/978-1-60761-416-6_2

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  • DOI: https://doi.org/10.1007/978-1-60761-416-6_2

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