Multiple myeloma and persistence of drug resistance in the age of novel drugs (Review)

• Published in: International journal of oncology Vol. 49; no. 1; pp. 33 - 50
• Main Authors: KRISHNAN, SABNA RAJEEV, JAISWAL, RITU, BROWN, ROSS D, LUK, FREDERICK, BEBAWY, MARY
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.07.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: ABC transporters; Antigens; Antineoplastic Agents - therapeutic use; Biopsy; Bone marrow; Cancer; Cell adhesion & migration; Cell cycle; combination therapy; Costs; Drug resistance; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - genetics; Drug therapy; Gene Expression Regulation, Neoplastic - drug effects; Hematology; Humans; Kinases; multidrug resistant clones; Multidrug resistant organisms; Multiple myeloma; Multiple Myeloma - blood; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Mutation; Neoplasm Proteins - blood; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Oncology, Experimental; Patients; personalized management; Pharmacology, Experimental; plasma cells; Proteins; relapse; Signal transduction; Urine
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2016.3516

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.