Role of HDAC isoforms and development of treatment of multiple myeloma using isoform-specific HDAC inhibitors

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  • 多発性骨髄腫におけるHDACアイソフォームの役割とその選択的阻害による治療法の開発
  • タハツセイ コツズイシュ ニ オケル HDAC アイソフォーム ノ ヤクワリ ト ソノ センタクテキ ソガイ ニ ヨル チリョウホウ ノ カイハツ

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Abstract

<p>Multiple myeloma (MM), which is derived from immunoglobulin-producing plasma cells, is treated using novel agents, such as proteasome inhibitors, immunomodulatory drugs (IMiDs), and anti-MM monoclonal antibodies, which have been developed based on preclinical findings. Although these treatments have improved MM prognosis, it still remains an incurable disease. Therefore, development of novel treatment strategies is warranted. Histone deacetylases (HDACs) are a group of deacetylating enzymes that catalyze the deacetylation of histone and non-histone proteins, leading to changes in gene expression and protein function and stability. Panobinostat, a pan-HDAC inhibitor, is now clinically available in combination with bortezomib and dexamethasone for the treatment of MM. To further improve treatment strategies for MM, HDACs are thought to have potential as next-generation therapeutics because HDAC isoform-selective inhibition, but not broad HDAC inhibition, is effective in MM cells. The roles of each HDAC isoform in MM are not yet precisely defined. To maintain or augment anti-MM effects without severe adverse reactions, preclinical and clinical studies are being undertaken to elucidate the impact of each HDAC isoform on MM and develop class- or isoform-selective HDAC inhibitors in combination with other therapeutics.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 60 (9), 1265-1274, 2019

    The Japanese Society of Hematology

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