Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3.

@article{Sun2014IntrinsicRT,
  title={Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3.},
  author={Chong Sun and Sebastijan Hobor and Andrea Bertotti and Davide Zecchin and Sidong Huang and Francesco Galimi and Francesca Cottino and Anirudh Prahallad and Wipawadee Grernrum and Anna Tzani and A Christine Schlicker and Lodewyk F. A. Wessels and Egbert F. Smit and Erik B Thunnissen and Pasi K Halonen and C. Lieftink and Roderick Leonardus Beijersbergen and Federica Di Nicolantonio and Alberto Bardelli and Livio Trusolino and Ren{\'e} Bernards},
  journal={Cell reports},
  year={2014},
  volume={7 1},
  pages={86-93}
}
There are no effective therapies for the ~30% of human malignancies with mutant RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that suppression of the ERBB3 receptor tyrosine kinase sensitizes KRAS mutant lung and colon cancer cells to MEK inhibitors. We show that MEK inhibition results in MYC-dependent transcriptional upregulation of ERBB3, which is responsible for intrinsic drug resistance. Drugs targeting both EGFR and ERBB2, each capable of forming heterodimers… CONTINUE READING
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