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

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 18; pp. 5068 - 5076
• Main Authors: Liu, Yan, Li, Yuyang, Wang, Xiaoen, Liu, Feiyang, Gao, Peng, Quinn, Max M, Li, Fei, Merlino, Ashley A, Benes, Cyril, Liu, Qingsong, Gray, Nathanael S, Wong, Kwok-Kin
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 15.09.2017
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Animal models; Animals; Antimetabolites, Antineoplastic - pharmacology; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Proliferation; Checkpoint Kinase 1 - antagonists & inhibitors; CHK1 protein; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; DNA damage; Drug Synergism; Drug Therapy, Combination; Female; Gemcitabine; Genetic engineering; Humans; K-Ras protein; LKB1 protein; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Metabolism; Mice; Mice, Knockout; Mice, Nude; Monoclonal antibodies; p53 Protein; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins p21(ras) - genetics; Targeted cancer therapy; Thiophenes - pharmacology; Tumor Cells, Cultured; Tumor suppressor genes; Tumor Suppressor Protein p53 - physiology; Tumors; Urea - analogs & derivatives; Urea - pharmacology; Xenograft Model Antitumor Assays

Cells lacking the tumor suppressor gene 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 cell lines and a genetically engineered mouse model of -induced lu...