Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations.

  title={Clinical Acquired Resistance to RAF Inhibitor Combinations in BRAF-Mutant Colorectal Cancer through MAPK Pathway Alterations.},
  author={Leanne G. Ahronian and Erin M. Sennott and Eliezer M Van Allen and Nikhil Wagle and Eunice Lee Kwak and Jason Edward Faris and Jason T Godfrey and Koki Nishimura and Kerry D Lynch and Craig Mermel and Elizabeth L. Lockerman and Anuj Kalsy and Joseph M Gurski and Samira Bahl and Kristin Anderka and Lisa M. Green and Niall J. Lennon and Tiffany G Huynh and Mari Mino-Kenudson and Gad Getz and Dora C Dias-Santagata and Anthony John Iafrate and Jeffrey A. Engelman and Levi A. Garraway and Ryan Bruce Corcoran},
  journal={Cancer discovery},
  volume={5 4},
UNLABELLED BRAF mutations occur in approximately 10% of colorectal cancers. Although RAF inhibitor monotherapy is highly effective in BRAF-mutant melanoma, response rates in BRAF-mutant colorectal cancer are poor. Recent clinical trials of combined RAF/EGFR or RAF/MEK inhibition have produced improved efficacy, but patients ultimately develop resistance. To identify molecular alterations driving clinical acquired resistance, we performed whole-exome sequencing on paired pretreatment and… CONTINUE READING
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