Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma

doi:10.1158/0008-5472.CAN-17-0567

CORC > 合肥物质科学研究院 > 中国科学院合肥物质科学研究院 > 中科院强磁场科学中心

	Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma
	Liu, Yan 1; Li, Yuyang 2; Wang, Xiaoen 1; Liu, Feiyang 3; Gao, Peng 1; Quinn, Max M.1; Li, Fei 1; Merlino, Ashley A.1; Benes, Cyril 4; Liu, Qingsong 3
刊名	CANCER RESEARCH
	2017-09-15
卷号	77 期号:18 页码:5068-5076
DOI	10.1158/0008-5472.CAN-17-0567
文献子类	Article
英文摘要	Cells lacking the tumor suppressor gene LKB1/STK11 alter their metabolism to match the demands of accelerated growth, leaving them highly vulnerable to stress. However, targeted therapy for LKB1-deficient cancers has yet to be reported. In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse model of Kras/p53/Lkb1-induced lung cancer, much higher rates of DNA damage occur, resulting in increased dependence on Chk1 checkpoint function. Here we demon-strate that short-term treatment with the Chk1 inhibitor AZD7762 reduces metabolism in pembrolizumab tumors, synergizing with the DNA-damaging drug gemcitabine to reduce tumor size in these models. Our results offer preclinical proof of concept for use of a Chk1 inhibitor to safely enhance the efficacy of gemcitabine, particularly in aggressive KRAS-driven LKB1-deficient lung adenocarcinomas. (C)2017 AACR.
WOS关键词	ADVANCED SOLID TUMORS ; THERAPEUTIC RESPONSE ; DOSE-ESCALATION ; CELL-GROWTH ; PHASE-I ; CANCER ; METABOLISM ; INACTIVATION ; AMPK ; CHECKPOINT
WOS研究方向	Oncology
语种	英语
WOS记录号	WOS:000410945700028
资助机构	National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; National Cancer Institute(R01 CA195740 ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA140594) ; 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Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant(SU2C-AACR-DT17-15) ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA163896 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA166480 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; CA122794 ; 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内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/33680]
专题	合肥物质科学研究院_中科院强磁场科学中心
作者单位	1.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA 2.Shandong Univ, Shandong Prov Hosp, Jinan, Shandong, Peoples R China 3.Chinese Acad Sci, High Field Magnet Lab, Hefei, Anhui, Peoples R China 4.Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA 5.Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA 6.NYU, Langone Med Ctr New York, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA
推荐引用方式 GB/T 7714	Liu, Yan,Li, Yuyang,Wang, Xiaoen,et al. Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma[J]. CANCER RESEARCH,2017,77(18):5068-5076.
APA	Liu, Yan.,Li, Yuyang.,Wang, Xiaoen.,Liu, Feiyang.,Gao, Peng.,...&Wong, Kwok-Kin.(2017).Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma.CANCER RESEARCH,77(18),5068-5076.
MLA	Liu, Yan,et al."Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma".CANCER RESEARCH 77.18(2017):5068-5076.