title: Environmental-mediated drug resistance: a target for multiple myeloma therapy.
abstract: Multiple myeloma is an incurable malignancy of mature clonal B cells. The refractory nature of this disease has long been attributed to the acquisition of drug resistance. Traditionally, mechanisms of drug resistance have been defined by genetic, acquired changes in the expression or function of specific genes products. However, over the past 10 years a large body of evidence has emerged demonstrating that in addition to mechanisms of drug resistance intrinsic to the cancer cell, there exist dynamic, de novo mechanisms coordinated by the tumor microenvironment resulting in a environmental-mediated drug resistance (EM-DR). Within this review we will provide an overview of some of these mechanisms of drug resistance and how they contribute to minimal residual disease and subsequent treatment failure. By understanding mechanisms of EM-DR, therapeutic targets can be identified and interventions designed to reduce minimal residual disease and improve clinical outcomes.
authors.affiliation: Departments of Experimental Therapeutics and Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA. ken.shain@moffitt.org
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Shain
authors.forename: William S
authors.initials: WS
authors.lastname: Dalton
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009101:Multiple Myeloma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D018365:Neoplasm, Residual / Q000139:chemically induced* / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects*; D017154:Stromal Cells / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins