Environmental-mediated drug resistance: a target for multiple myeloma therapy.

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.