American Association for Cancer Research
00085472can211547-sup-265813_2_supp_7460018_r0v2bw.pdf (924.91 kB)

Figure S3 from A Dual PI3K/HDAC Inhibitor Induces Immunogenic Ferroptosis to Potentiate Cancer Immune Checkpoint Therapy

Download (924.91 kB)
journal contribution
posted on 2023-03-31, 04:45 authored by Fushun Fan, Pei Liu, Rudi Bao, Jian Chen, Minhua Zhou, Zhenxian Mo, Yaru Ma, Haiqi Liu, Yiping Zhou, Xiong Cai, Changgeng Qian, Xinjian Liu

Transcriptional profiling, cell cycle arrest and apoptosis of BEBT-908 treated tumor cells.


National Science and Technology Major Project of China

Guangdong Pearl River Talents Plan

Guangzhou Municipal Science and Technology Project

Guangdong Basic and Applied Basic Research Foundation

Shenzhen Science and Technology Program

Fundamental Research Funds for the Central Universities



The capacity of targeted anticancer agents to exert immunomodulatory effects provides a strong rationale to develop novel agents suitable for combinatorial regimens with immunotherapy to improve clinical outcomes. In this study, we developed a dual-targeting PI3K and HDAC inhibitor BEBT-908 that potently inhibits tumor cell growth and potentiates anti-PD1 therapy in mice by inducing immunogenic ferroptosis in cancer cells. Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. Furthermore, BEBT-908 promoted a proinflammatory tumor microenvironment that activated host antitumor immune responses and potentiated immune checkpoint blockade therapy. Mechanistically, BEBT-908–induced ferroptosis led to upregulation of MHC class I and activation of endogenous IFNγ signaling in cancer cells via the STAT1 signaling pathway. The dual PI3K/HDAC inhibitor BEBT-908 is a promising targeted therapeutic agent against multiple cancer types that promotes immunogenic ferroptosis and enhances the efficacy of immunotherapy. The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of tumor cells and potentiating cancer immunotherapy.