Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer

@article{Duncan2012DynamicRO,
  title={Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer},
  author={James S. Duncan and Martin C. Whittle and Kazuhiro Nakamura and Amy N. Abell and Alicia A. Midland and Jon S. Zawistowski and Nancy Lassignal Johnson and Deborah A. Granger and Nicole Vincent Jordan and David Brian Darr and Jerry E. Usary and Pei-fen Kuan and David M. Smalley and B. J. Major and Xiaping He and Katherine A Hoadley and Bing Zhou and Norman E Sharpless and Charles M. Perou and William Y. Kim and Shawn M. Gomez and Xin Mao Chen and Jian Jin and Stephen V Frye and H. Shelton Earp and Lee M Graves and Gary Leon Johnson},
  journal={Cell},
  year={2012},
  volume={149},
  pages={307-321}
}
Kinase inhibitors have limited success in cancer treatment because tumors circumvent their action. Using a quantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple-negative breast cancer (TNBC) cells and genetically engineered mice (GEMMs). MEK inhibition caused acute ERK activity loss, resulting in rapid c-Myc degradation that induced expression and activation of several receptor tyrosine kinases (RTKs). RNAi knockdown of ERK or c-Myc mimicked RTK… CONTINUE READING