RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

@article{Hatzivassiliou2010RAFIP,
  title={RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth},
  author={Georgia Hatzivassiliou and Kyung Hee Song and I. Ling Yen and Barbara J. Brandhuber and Daniel J. Anderson and Ryan Alvarado and Mary J. C. Ludlam and David Stokoe and Susan L. Gloor and Guy P. A. Vigers and Tony H Morales and Ignacio Aliagas and Bonnie Rui Liu and Steve Sideris and Klaus P. Hoeflich and Bijay S. Jaiswal and Somasekar Seshagiri and Hartmut Koeppen and Marcia Belvin and Lori S. Friedman and Shiva Malek},
  journal={Nature},
  year={2010},
  volume={464},
  pages={431-435}
}
Activating mutations in KRAS and BRAF are found in more than 30% of all human tumours and 40% of melanoma, respectively, thus targeting this pathway could have broad therapeutic effects. Small molecule ATP-competitive RAF kinase inhibitors have potent antitumour effects on mutant BRAF(V600E) tumours but, in contrast to mitogen-activated protein kinase kinase (MEK) inhibitors, are not potent against RAS mutant tumour models, despite RAF functioning as a key effector downstream of RAS and… CONTINUE READING
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