Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

Abstract

Epigenetic alterations frequently participate in the onset of hematological malignancies. Histone deacetylases (HDACs) are essential for regulating gene transcription and various signaling pathways. Targeting HDACs has become a novel treatment option for hematological malignancies. Chidamide is the first oral selective HDAC inhibitor for HDAC1, HDAC2, HDAC3, and HDAC10 and was first approved for the treatment of R/R peripheral T‐cell lymphoma by the China Food and Drug Administration in 2014. Chidamide was also approved under the name Hiyasta (HBI‐8000) in Japan in 2021. In vitro studies revealed that chidamide could inhibit proliferation and induce apoptosis via cell cycle arrest and the regulation of apoptotic proteins. In clinical studies, chidamide was also efficacious in multiple myeloma, acute leukemia and myelodysplastic syndrome. This review includes reported experimental and clinical data on chidamide monotherapy or chidamide treatment in combination with chemotherapy for various hematological malignancies, offering a rationale for the renewed exploration of this drug.

A short report of novel acute promyelocytic leukemia with runt‐related transcription factor 1‐retinoic acid receptor alpha

“…The nuclear receptor corepressor complex and silencing mediator of RA were found to bind to HDAC3, negatively regulating RUNX1 target genes to prevent myeloid differentiation, and thus resulting in cellular transformation. 6 In conclusion, we describe here a first report of variant APL with…”

The efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of hemophagocytic lymphohistiocytosis in adult patients: an open-label, single-center study

“…Chidamide is an oral selective histone deacetylase (HDAC) inhibitor that selectively inhibits HDAC1, HDAC2, HDAC3, and HDAC10, inducing apoptosis and growth arrest in leukemia cells. It has been approved for the treatment of relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) ( 22 ) and is currently being studied for use in other leukemia and myelodysplastic syndromes (MDS) ( 23 , 24 ). Chidamide’s anti-inflammatory effect may be due to its ability to inhibit the NF-κB signaling pathway, which is involved in the body’s inflammatory and immune responses ( Figure 4 ).…”

The clinical regimens and cell membrane camouflaged nanodrug delivery systems in hematologic malignancies treatment

“…Clinical DNA hypomethylating agents (HMAs) in HMs therapy mainly include azacitidine ( Odenike, 2017 ), decitabine ( Santos et al, 2010 ), guadecitabine ( Kantarjian et al, 2017 ) and ASTX727 (cedazuridine/decitabine) ( Abuasab et al, 2022 ). Common HDAC inhibitors used for clinical trials in HMs treatment include vorinostat ( Hopfinger et al, 2014 ), belinostat ( Johnston et al, 2021 ), panobinostat ( El Omari et al, 2023 ), chidamide ( Cao et al, 2023 ), and romidepsin ( Bates et al, 2015 ). As the core member of the BET family, BRD4 regulates gene expression, and its inhibitors, such as JQ1 ( Pericole et al, 2019 ) and AZD5153 ( Rhyasen et al, 2016 ), are also potential clinical drugs in HMs therapy.…”