1. GCS-100 selectively kills KRAS-addicted lung tumors.
GCS-100 selectively kills KRAS-addicted lung tumors. A, Mice with established subcutaneous KRAS-mutant lung PDX-8 tumors were treated with vehicle (n = 9) or GCS-100 (n = 10; 20 mg/kg i.p. 3 times per week) for 15 days. Change in tumor volume vs. time (left) and after 15 days of treatment (right). B, Sections from PDX-8 tumors were stained for TUNEL as an indicator of apoptosis, and the percent of TUNEL+ cells quantified using ImageJ. Scale bar, 50 μm. C, LSL-KrasG12D mice were infected with Adeno-Cre via intratracheal injection. After 3 months, sections of lung tissue reveal β3-expressing tumors with areas of adenoma, dysplasia, and adenocarcinoma. Scale bars, 50 μm. D and E, Mice were randomized and treated with either vehicle control or GCS-100 for 1 additional month. Representative histologic images show lung tumor burden. Scale bar, 2 mm, and 500 μm for inset. Tumor burden (tumor area as a percentage of total lung area) in LSL-KrasG12D mice treated with vehicle (n = 7) or GCS-100 (n = 7) at a dose of 20 mg/kg i.p. 3 times per week. Table shows effect of the drug on tumor histopathology. F, Effect of GCS-100 on apoptosis, evaluated using TUNEL staining by IHC. Scale bar, 50 μm. All data represent mean ± SD from at least three independent experiments. Statistical significance was determined by the Student t test. **, P < 0.01; ***, P <
Laetitia Seguin et al. Cancer Discov 2017;7:
©2017 by American Association for Cancer Research