Bromodomain and extra-terminal (BET) inhibitors in treating myeloid neoplasms

Abstract

With improved understanding of the epigenetic alterations underlying cancer development, numerous novel agents targeting pathways involved in epigenetic modifications and transcription including bromodomain inhibitors are under active investigation. We aim to discuss epigenetic modulation with a focus on bromodomain extra-terminal inhibitors (BETi) in the treatment of myeloid neoplasms. Since the first proof-of-concept description of BETi synthesis and its antineoplastic effect, approximately 20 BETi have been generated and many of them are studied in the context of cancer treatment. Emerging pre-clinical and early clinical studies suggest that BETi may have activity in the management of many hematological malignancies including acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), myeloproliferative neoplasm (MPNs), and lymphoma. We comprehensively reviewed and summarized preclinical and clinical data on BETi in treating myeloid neoplasms.

Keywords:

• Cancer
• myeloid neoplasm
• BET inhibitors
• epigenetics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

NP: Consulting/honorarium: Celgene; Stemline; Incyte; Novartis; MustangBio; Roche Diagnostics, LFB, Pacylex

Research funding/clinical trials support: Stemline; Novartis; Abbvie; Samus; Cellectis; Plexxikon; Daiichi-Sankyo; Affymetrix, SagerStrong Foundation

GB: Advisory/honorarium: Treadwell Therapeutics; Nkarta Therapeutics; BioTheryX; BioLine Rx; PTC Therapeutics; Argenx; FTC Therapeutics; Curio Science LLC

Research funding/clinical trials support: Oncoceutics; Xbiotech USA; Arvinas; Polaris; AstraZeneca; BMS; BioLineRx; Cyclacel; GSK; Janssen; Incyte; AbbVie; Novartis.

Additional information

Funding

This research is supported in part by the M. D. Anderson Cancer Center Support Grant P30 CA016672 and the SagerStrong Foundation.