Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression.

@article{Hayes2016LongTermEI,
  title={Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression.},
  author={Tikvah K. Hayes and Nicole F. Neel and Chaoxin Hu and Prson Gautam and Melissa Chenard and Brian George Long and Meraj Aziz and Michelle Kimberly Kassner and Kirsten L Bryant and Mariaelena Pierobon and Raoud Marayati and Swapnil Kher and Samuel D. George and Mai Xu and Andrea Wang-Gillam and Ahmed A. Samatar and Anirban Maitra and Krister Wennerberg and Emanuel F Petricoin and Hongwei Holly Yin and Barry D. Nelkin and Adrienne D. Cox and Jen Jen J. Yeh and Channing J Der},
  journal={Cancer cell},
  year={2016},
  volume={29 1},
  pages={
          75-89
        }
}
Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death. Additional combinations that enhanced ERK inhibitor action were also identified. Unexpectedly, long-term treatment of sensitive… CONTINUE READING
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