American Association for Cancer Research
00085472can170567-sup-179489_2_supp_4153362_ksxy19.pptx (285.25 kB)

S-Figure-2 from Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma

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posted on 2023-03-31, 00:42 authored by Yan Liu, Yuyang Li, Xiaoen Wang, Feiyang Liu, Peng Gao, Max M. Quinn, Fei Li, Ashley A. Merlino, Cyril Benes, Qingsong Liu, Nathanael S. Gray, Kwok-Kin Wong

FACS analysis of GFP positive Lkb1-null t4 cells carrying resistant Chek1


National Cancer Institute

American Association for Cancer Research



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 demonstrate 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. Cancer Res; 77(18); 5068–76. ©2017 AACR.