The Multidrug Resistance Mechanisms and their Interactions with the Radiopharmaceutical Probes Used for an In Vivo Detection

Authors: Perek N.; Denoyer D.

Source: Current Drug Metabolism, Volume 3, Number 1, February 2002 , pp. 97-113(17)

Publisher: Bentham Science Publishers

Abstract:

The resistance of human malignancy to multiple chemotherapeutic agents ts remains a major obstacle in cancer therapy. This resistance phenomenon is called ”multiple“ because when cells are resistant they fail to respond to any of a wide range of anticancer agents. This leads to a complete ineffectiveness of any treatment and has dramatic consequences for the patients. This chemoresistance can be intrinsic -when tumour cells do not respond initially to the treatment- or acquired -when resistance appear during the therapy. Our understanding of the mechanisms responsible of the drug resistance has increased over the past few years. The tumour resistance is able to develop several strategies to inactivate the chemotherapeutic agents such as activation of the detoxification process, and overexpression of efflux pump proteins. The phenotype resistance of the cell is mainly characterised by an increased expression of membrane transport proteins such as the P-glycoprotein and the Multidrug Resistance Protein - MRP1 - that act as real efflux pump to anticancer agent and contribute to physiological alterations i.e. intracellular pH and plasma membrane potentials. The detoxification procedure is also implicated with the Glutathione S transferase enzymes and the major anti oxidant of the cells the glutathione (GSH). More recently a newly reported transporter called ”Breast Resistance Cancer Protein“ has appeared. The role of all these transporters and the link with the detoxification systems in the clinical outcome of cancer chemotherapy is the subject of intense research. Particularly, one way of interest concerned in vivo investigations with radiolabelled compounds used in nuclear medicine. The understanding of how the radiolabelled compounds could interact with the phenotype resistance of the cells had a key role for further exploration of molecular imaging of the MDR phenotype.

Keywords: Radiopharmaceutical Probes; glutathione (GSH); Glutathione S-Transferase (GST); P-Glycoprotein; cyclosporin

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200023338107

Publication date: 2002-02-01

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

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• In this Subject: Anatomy & Physiology ,  Pharmacology
• By this author: Perek N. ;  Denoyer D.

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