title: Drug metabolism and clearance system in tumor cells of patients with multiple myeloma.
abstract: Resistance to chemotherapy is a major limitation of cancer treatments with several molecular mechanisms involved, in particular altered local drug metabolism and detoxification process. The role of drug metabolism and clearance system has not been satisfactorily investigated in Multiple Myeloma (MM), a malignant plasma cell cancer for which a majority of patients escapes treatment. The expression of 350 genes encoding for uptake carriers, xenobiotic receptors, phase I and II Drug Metabolizing Enzymes (DMEs) and efflux transporters was interrogated in MM cells (MMCs) of newly-diagnosed patients in relation to their event free survival. MMCs of patients with a favourable outcome have an increased expression of genes coding for xenobiotic receptors (RXRα, LXR, CAR and FXR) and accordingly of their gene targets, influx transporters and phase I/II DMEs. On the contrary, MMCs of patients with unfavourable outcome displayed a global down regulation of genes coding for xenobiotic receptors and the downstream detoxification genes but had a high expression of genes coding for ARNT and Nrf2 pathways and ABC transporters. Altogether, these data suggests ARNT and Nrf2 pathways could be involved in MM primary resistance and that targeting RXRα, PXR, LXR and FXR through agonists could open new perspectives to alleviate or reverse MM drug resistance.
authors: Institute of Human Genetics, CNRS-UPR1142, Montpellier, France.|High Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
authors: Wafa
authors: W
authors: Hassen
authors: Institute of Human Genetics, CNRS-UPR1142, Montpellier, France.|CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Haematology, Montpellier, France.
authors: Alboukadel
authors: A
authors: Kassambara
authors: Institute of Human Genetics, CNRS-UPR1142, Montpellier, France.|CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Haematology, Montpellier, France.
authors: Thierry
authors: T
authors: Reme
authors: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, UK.
authors: Surinder
authors: S
authors: Sahota
authors: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.|Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
authors: Anja
authors: A
authors: Seckinger
authors: CHU Montpellier, Department of Clinical Hematology, Montpellier, France.
authors: Laure
authors: L
authors: Vincent
authors: CHU Montpellier, Department of Clinical Hematology, Montpellier, France.
authors: Guillaume
authors: G
authors: Cartron
authors: Institute of Human Genetics, CNRS-UPR1142, Montpellier, France.|CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Haematology, Montpellier, France.|University of Montpellier 1, UFR Medicine, Montpellier, France.
authors: Jérôme
authors: J
authors: Moreaux
authors: Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.|Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany.
authors: Dirk
authors: D
authors: Hose
authors: Institute of Human Genetics, CNRS-UPR1142, Montpellier, France.|CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biological Haematology, Montpellier, France.|University of Montpellier 1, UFR Medicine, Montpellier, France.
authors: Bernard
authors: B
authors: Klein
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins
keywords: drug metabolism and clearance; multiple myeloma; prognosis