B-cell Lymphoma 6 Inhibitors: Current Advances and Prospects of Drug Development for Diffuse Large B-cell Lymphomas

B-cell lymphoma 6 (BCL6) is a transcriptional repressor that regulates the differentiation of B lymphocytes and mediates the formation of germinal centers (GCs) by recruiting corepressors through the BTB domain of BCL6. Physiological processes regulated by BCL6 involve cell activation, differentiation, DNA damage, and apoptosis. BCL6 is highly expressed when the gene is mutated, leading to the malignant proliferation of cells and drives tumorigenesis. BCL6 overexpression is closely correlated with tumorigenesis in diffuse large B-cell lymphoma (DLBCL) and other lymphomas, and BCL6 inhibitors can effectively inhibit some lymphomas and overcome resistance. Therefore, targeting BCL6 might be a promising therapeutic strategy for treating lymphomas. Herein, we comprehensively review the latest development of BCL6 inhibitors in diffuse large B-cell lymphoma and discuss the overview of the pharmacophores of BCL6 inhibitors and their efficacies in vitro and in vivo. Additionally, the current advances in BCL6 degraders are provided.

Automated summary

B-cell lymphoma 6 (BCL6) is a transcriptional repressor that is highly expressed in malignant cells and drives tumorigenesis. Targeting BCL6 may be a promising therapeutic strategy for treating lymphomas. This review comprehensively discusses the latest development of BCL6 inhibitors in diffuse large B-cell lymphoma, including their pharmacophores and efficacies.