Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance.
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ABSTRACT:
SUBMITTER: Ali M
PROVIDER: S-EPMC5472712 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance.
Ali Moiez M Kaltenbrun Erin E Anderson Gray R GR Stephens Sarah Jo SJ Arena Sabrina S Bardelli Alberto A Counter Christopher M CM Wood Kris C KC
Nature communications 20170608
KRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demons ...[more]
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