title: Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review).
abstract: Multiple myeloma (MM) is a mature B cell neoplasm that results in multi-organ failure. The median age of onset, diverse clinical manifestations, heterogeneous survival rate, clonal evolution, intrinsic and acquired drug resistance have impact on the therapeutic management of the disease. Specifically, the emergence of multidrug resistance (MDR) during the course of treatment contributes significantly to treatment failure. The introduction of the immunomodulatory agents and proteasome inhibitors has seen an increase in overall patient survival, however, for the majority of patients, relapse remains inevitable with evidence that these agents, like the conventional chemotherapeutics are also subject to the development of MDR. Clinical management of patients with MM is currently compromised by lack of a suitable procedure to monitor the development of clinical drug resistance in individual patients. The current MM prognostic measures fail to pick the clonotypic tumor cells overexpressing drug efflux pumps, and invasive biopsy is insufficient in detecting sporadic tumors in the skeletal system. This review summarizes the challenges associated with treating the complex disease spectrum of myeloma, with an emphasis on the role of deleterious multidrug resistant clones orchestrating relapse.
authors.affiliation: Graduate School of Health, Discipline of Pharmacy, University of Technology, Sydney, NSW 2007, Australia.
authors.forename: Sabna Rajeev
authors.initials: SR
authors.lastname: Krishnan
authors.affiliation: Graduate School of Health, Discipline of Pharmacy, University of Technology, Sydney, NSW 2007, Australia.
authors.forename: Ritu
authors.initials: R
authors.lastname: Jaiswal
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Brown
authors.affiliation: Graduate School of Health, Discipline of Pharmacy, University of Technology, Sydney, NSW 2007, Australia.
authors.forename: Frederick
authors.initials: F
authors.lastname: Luk
authors.affiliation: Graduate School of Health, Discipline of Pharmacy, University of Technology, Sydney, NSW 2007, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Bebawy
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009363:Neoplasm Proteins / Q000097:blood; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins