Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma
Year: 2017
Type: article
Abstract: 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.
Source: Cancer Research
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1058243294, MUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung Cancer, In vivo analysis of EGFR mutant driven lung cancers responses to radiation therap, Targeting the transcriptional and epigenetic landscape in chemo-refractory Small-Cell Lung Cancer, Therapeutic approaches for LKB1-deficient non-small cell lung cancer, Credentialing Mouse Models for Immune System Therapy Research, Therapeutic strategies for specific subsets of KRAS mutant lung cancers, G77253623, In vivo murine models of metastasis for therapeutic testing
OpenAlex ID: W2741613334