Histone Deacetylase Inhibitors in Multiple Myeloma: Rationale and Evidence for Their Use in Combination Therapy.

Histone Deacetylase Inhibitors in Multiple Myeloma: Rationale and Evidence for Their Use in Combination Therapy. Clin Lymphoma Myeloma Leuk. 2013 Jun 17; Authors: Kaufman JL, Fabre C, Lonial S, Richardson PG Abstract Multiple myeloma (MM) arises from abnormal proliferation and survival (ie, a high proliferative index and a low apoptotic index) of mature immunoglobulin-producing plasma cells in the bone marrow. Development of novel therapeutic options, such as proteasome inhibitors and immunomodulatory agents (IMiDs), has improved treatment outcomes. However, patients often develop relapsed and refractory MM, thus requiring alternative treatment approaches. Histone acetyltransferases and histone deacetylases (HDACs) control the acetylation status of proteins and affect a broad array of physiologic processes (eg, cell cycle, apoptosis, and protein folding) involved in cell growth and survival. The discovery that HDACs might have a role in various hematologic malignancies, including MM, has led to the development of HDAC inhibitors as potential antitumor agents. Preclinical evidence from studies of HDAC inhibitors in combination with proteasome inhibitors (eg, bortezomib and carfilzomib), other antimyeloma agents, including IMiDs (eg, lenalidomide), and cytotoxic agents (eg, melphalan, pegylated liposomal doxorubicin), provides a strong scientific rationale for the evaluation of these regimens. Results from early stage clinical trials further sup...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Lymphoma Myeloma Leuk Source Type: research