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    A Novel BCL-2 Inhibitor APG-2575 Exerts Synthetic Lethality With BTK or MDM2-p53 Inhibitor in Diffuse Large B-Cell Lymphoma

    Qiuyun Luo*†1, Wentao Pan*†‡1, Suna Zhou*†1, Guangfeng Wang, Hanjie Yi, Lin Zhang, Xianglei Yan*†, Luping Yuan*†, Zhenyi Liu#, Jing Wang**, Haibo Chen#, MiaoZhen Qiu*††, DaJun Yang*†‡, Jian Sun*‡‡

    Oncology Research, Vol.28, No.4, pp. 331-344, 2020, DOI:10.3727/096504020X15825405463920

    Abstract Despite therapeutic advances, the effective treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) remains a major clinical challenge. Evasion of apoptosis through upregulating antiapoptotic B-cell lymphoma-2 (BCL-2) family members and p53 inactivation, and abnormal activation of B-cell receptor signaling pathway are two important pathogenic factors for DLBCL. In this study, our aim is to explore a rational combination of BCL-2 inhibitor plus Bruton’s tyrosine kinase (BTK) blockade or p53 activation for treating DLBCL with the above characteristics. We demonstrated that a novel BCL-2 selective inhibitor APG-2575 effectively suppressed DLBCL with BCL-2 high expression via activating the mitochondrial apoptosis… More >

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