New insights into possible HDAC inhibitor resistance in DLBCL - Comment on 'defining cellular responses to HDAC-selective inhibitors reveals that efficient targeting of HDAC3 is required to elicit cytotoxicity and overcome naïve resistance to pan-HDACi in diffuse large B cell lymphoma' by Havas et al

Transl Oncol. 2024 Jun:44:101820. doi: 10.1016/j.tranon.2023.101820. Epub 2023 Nov 15.

¹ Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; Department of Internal Medicine I, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria. Electronic address: tobias.kiesslich@pmu.ac.at.
² Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria; Department of Internal Medicine I, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria. Electronic address: christian.mayr@pmu.ac.at.
³ Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria. Electronic address: dino.bekric@pmu.ac.at.
⁴ Institute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), 5020 Salzburg, Austria; Cancer Cluster Salzburg, 5020 Salzburg, Austria. Electronic address: d.neureiter@salk.at.

Abstract

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This editorial provides a brief overview of the role of HDACs in diffuse large B-cell lymphoma (DLBCL).
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Possible mechanisms of HDAC inhibitor resistance in DLBCL are discussed in detail.
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It highlights the need for developing HDAC isoform-specific inhibitors.
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Additional combinatory regimens and dual-specificity inhibitors may increase the therapeutic efficacy of HDAC inhibition in this aggressive lymphoma.

Keywords: DLBCL; Epigenetics; Histone deacetylation; Histone deacetylation inhibitors; Resistance mechanism.