Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance

Moiez Ali; Erin Kaltenbrun; Grace R. Anderson; Sarah Jo Stephens; Sabrina Arena; Alberto Bardelli; Christopher M. Counter; Kris C. Wood

doi:10.1038/ncomms15617

Nature Communications (Jun 2017)

Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance

Moiez Ali,
Erin Kaltenbrun,
Grace R. Anderson,
Sarah Jo Stephens,
Sabrina Arena,
Alberto Bardelli,
Christopher M. Counter,
Kris C. Wood

Affiliations

Moiez Ali: Department of Pharmacology and Cancer Biology, Duke University
Erin Kaltenbrun: Department of Pharmacology and Cancer Biology, Duke University
Grace R. Anderson: Department of Pharmacology and Cancer Biology, Duke University
Sarah Jo Stephens: Department of Pharmacology and Cancer Biology, Duke University
Sabrina Arena: Department of Oncology, University of Torino
Alberto Bardelli: Department of Oncology, University of Torino
Christopher M. Counter: Department of Pharmacology and Cancer Biology, Duke University
Kris C. Wood: Department of Pharmacology and Cancer Biology, Duke University

DOI: https://doi.org/10.1038/ncomms15617
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 11

Abstract

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KRAS mutations drive resistance to diverse targeted therapies. In this study, the authors show that the rare codons of KRAS, yielding low oncogene expression, can be overcome to drive resistance to anti-EGFR therapy in CRC through upregulation of global translation or through selection of more potent KRASQ61mutations.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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