| First Author | Liu Y | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 18 | Pages | 5068-5076 |
| PubMed ID | 28754670 | Mgi Jnum | J:245578 |
| Mgi Id | MGI:5919890 | Doi | 10.1158/0008-5472.CAN-17-0567 |
| Citation | Liu Y, et al. (2017) Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma. Cancer Res 77(18):5068-5076 |
| abstractText | 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. (c)2017 AACR. |
