MPT0G413, A Novel HDAC6-Selective Inhibitor, and Bortezomib Synergistically Exert Anti-tumor Activity in Multiple Myeloma Cells

In conclusion, MPT0G413 and BTZ synergistically inhibit MM viability, providing a framework for the clinical evaluation of combined therapies for MM. Introduction Multiple myeloma (MM) is a B cell malignancy characterized by the proliferation of bone marrow (BM) plasma cells and the production of large amounts of abnormal immunoglobulins (1) In the United States, it was estimated that 30,770 new MM cases would be diagnosed in 2018, accounting for 1.8% of newly diagnosed cancer cases (2). Furthermore, 12,770 MM-related deaths in 2018 accounted for an estimated 2.1% of all cancer deaths (2). In the past decade, MM treatment outcomes have improved since the approval of thalidomide-related immunomodulatory drugs and the proteasome inhibitor bortezomib by the FDA. Although MM patients have exhibited good responses to these agents (3), the incidence of relapse remains high (4, 5). Therefore, new agents are needed to ensure better long-term outcomes for such patients. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysines of histones and thus, act as gene transcription regulators (6). HDACs are considered attractive cancer therapeutic targets because changes in histone modification are frequently observed in human cancers, including MM. Accordingly, four small-molecule pan-HDAC inhibitors have been introduced for hematologic malignancies (7, 8). Recent clinical studies have evaluated the use of pan-HDAC inhibitors, such as vorinostat (suberoylanili...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research