A kinome wide CRISPR/Cas9 screen uncovers novel resistance factors to MEK inhibition in colorectal cancer
T Zhan, D Brüggemann, F Heigwer, M Breinig, J Winter, S Leible, M Ebert, M Boutros · Zeitschrift für Gastroenterologie · 2015 · Heft 08
Bibliografische Angaben
Zusammenfassung
Einleitung: The Ras/MEK/ERK pathway is frequently mutated in colorectal cancer (CRC) and KRAS mutations present a major therapeutic challenge. Attempts to inhibit downstream effectors of KRAS including MEK revealed only modest clinical efficiency. The mechanisms by which CRC with KRAS mutation acquires resistance to MEK inhibition are not completely understood. Pooled CRISPR/Cas9 screens offer a novel high-throughput method for functional characterization of genes by generating knockouts and can be used to identify mechanisms of drug resistance. Methodik: A pooled, kinome-wide knockout library of KRAS mutant CRC…