The research outcomes of our company’s First-In-Class drug BEBT-908  have been published as a research paper "A Dual PI3K/HDAC Inhibitor Induces Immunogenic Ferroptosis to Potentiate Cancer Immune Checkpoint Therapy" (PI3K/HDAC dual-target inhibitor strengthens tumors by inducing immunogenic ferroptosis Immune checkpoint therapy) online in the top international academic journal "CANCER RESEARCH" (IF=12.7) on October 28, 2021. 

This article systematically explains the anti-tumor mechanism of BEBT-908, which provides a theoretical basis for the treatment of advanced solid tumors in combination with PD1/PD-L1 monoclonal antibody.

The ability of anticancer targeted drugs to mediate immunomodulatory effects provides a strong rationale for the development of novel drugs suitable for immunotherapy combination regimens. In this study, we found that the dual-target PI3K and HDAC inhibitor BEBT-908 effectively inhibited tumor cell growth and enhanced anti-PD1 immunotherapy in mouse colorectal cancer by inducing immunogenic ferroptosis in cancer cells. Studies have found that BEBT-908 promotes ferroptosis in cancer cells by acetylating p53 and promoting the expression of ferroptosis signaling. Furthermore, BEBT-908 promotes a pro-inflammatory tumor microenvironment, activates host antitumor immune responses and enhances immune checkpoint blockade therapy. Mechanistically, BEBT-908-induced ferroptosis leads to major histocompatibility complex class I (MHC I) upregulation and activation of endogenous interferon gamma (IFNγ) signaling in cancer cells through the STAT1 signaling pathway. The dual-target PI3K/HDAC inhibitor BEBT-908 is a promising targeted therapy for multiple cancer types, promoting immunogenic ferroptosis and enhancing the efficacy of immunotherapy. 

A schematic diagram illustrating BEBT-908 mediated ferroptosis and stimulation of pro-inflammatory pathways.

 论文链接：https://cancerres.aacrjournals.org/content/early/2021/10/27/0008-5472.CAN-21-1547