BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL-2 expression.

ABSTRACT: Although the MYC oncogenic network represents an attractive therapeutic target for lymphoma, MYC inhibitors have been difficult to develop. Alternatively, inhibitors of epigenetic/ transcriptional regulators, particularly the bromodomain and extraterminal (BET) family, have been used to modulate MYC. However, current benzodiazepine-derivative BET inhibitors (BETi) elicit disappointing responses and dose-limiting toxicity in relapsed/refractory lymphoma, potentially because of enrichment of high-risk molecular features and chemical backbone-associated toxicities. Consequently, novel nonbenzodiazepine BETi and improved mechanistic understanding are required. Here we characterize the responses of aggressive MYC-driven lymphomas to 2 nonbenzodiazepine BETi: PLX51107 and PLX2853. Both invoked B

SUBMITTER: Cummin TEC 

PROVIDER: S-EPMC7391160 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature