國家衛生研究院 NHRI:Item 3990099045/13316
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    题名: A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment
    作者: Song, JS;Chang, CC;Wu, CH;Dinh, TK;Jan, JJ;Huang, KW;Chou, MC;Shiue, TY;Yeh, KC;Ke, YY;Yeh, TK;Ta, YNN;Lee, CJ;Huang, JK;Sung, YC;Shia, KS;Chen, Y
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti–PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.
    日期: 2021-03-30
    關聯: Proceedings of the National Academy of Sciences of the United States of America. 2021 Mar 30;118(13):Article number e2015433118.
    Link to: http://dx.doi.org/10.1073/pnas.2015433118
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000637394200021
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85103063097
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