气候变化领域集成服务门户(CCPortal): A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment

CCPortal

DOI	10.1073/pnas.2015433118
	A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment
	Song J.-S.; Chang C.-C.; Wu C.-H.; Dinh T.K.; Jan J.-J.; Huang K.-W.; Chou M.-C.; Shiue T.-Y.; Yeh K.-C.; Ke Y.-Y.; Yeh T.-K.; Ta Y.-N.N.; Lee C.-J.; Huang J.-K.; Sung Y.-C.; Shia K.-S.; Chen Y.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CXCR4 receptor; Hepatocellular carcinoma; Programmed cell death 1; Sorafenib; Tumor microenvironment
语种	英语
scopus关键词	antineoplastic agent; bprcx 807; chemokine receptor CXCR4 antagonist; plerixafor; programmed death 1 receptor; programmed death 1 receptor antagonist; sorafenib; unclassified drug; angiogenesis; animal cell; animal experiment; animal model; animal tissue; area under the curve; Article; cancer chemotherapy; cancer growth; cancer inhibition; cell infiltration; cell migration; controlled study; cytotoxic T lymphocyte; distant metastasis; drug efficacy; drug half life; drug potency; drug potentiation; drug safety; drug selectivity; drug structure; immune deficiency; immunostimulation; in vitro study; in vivo study; life expectancy; liver cell carcinoma; male; mouse; nonhuman; nuclear reprogramming; overall survival; phenotype; priority journal; rat; tumor microenvironment; tumor-associated macrophage
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180056
作者单位	Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, 35053, Taiwan; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, 30013, Taiwan
推荐引用方式 GB/T 7714	Song J.-S.,Chang C.-C.,Wu C.-H.,et al. A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment[J],2021,118(13).
APA	Song J.-S..,Chang C.-C..,Wu C.-H..,Dinh T.K..,Jan J.-J..,...&Chen Y..(2021).A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Song J.-S.,et al."A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).