New, next-generation targeted treatment strategies are required to improve outcomes in patients with multiple myeloma (MM). Monoclonal antibodies, cell signaling inhibitors, and selective therapies targeting the bone marrow microenvironment have demonstrated encouraging results with generally manageable toxicity in therapeutic trials of patients with relapsed and refractory disease, each critically informed by preclinical studies. A combination approach of these newer agents with immunomodulators and/or proteasome inhibitors as part of a treatment platform seems to improve the efficacy of anti-MM regimens, even in heavily pretreated patients. Future studies are required to better understand the complex mechanisms of drug resistance in MM.
Keywords: BET bromodomain inhibitors; Deubiquitinating enzyme inhibitors; Heat shock protein 90 inhibitors; Histone deacetylase inhibitors; Multiple myeloma; PIK3/Akt/mTOR inhibitors; Second-generation proteasome inhibitors; Wnt.
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