Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy.

doi:10.1158/0008-5472.CAN-23-2729

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Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy.

Cancer research - 15 Dec 2023

Mukhopadhyay Suman, Huang Hsin-Yi, Lin Ziyan, Ranieri Michela, Li Shuai, Sahu Soumyadip, Liu Yingzhuo, Ban Yi, Guidry Kayla, Hu Hai, Lopez Alfonso, Sherman Fiona, Tan Yi Jer, Lee Yeuan Ting, Armstrong Amanda P, Dolgalev Igor, Sahu Priyanka, Zhang Tinghu, Lu Wenchao, Gray Nathanael S, Christensen James G, Tang Tracy T, Velcheti Vamsidhar, Khodadadi-Jamayran Alireza, Wong Kwok-Kin, Neel Benjamin G

Abstract excerpt

Non-small lung cancers (NSCLC) frequently (∼30%) harbor KRAS driver mutations, half of which are KRASG12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is particularly refractory to conventional, targeted, and immune therapy. Development of KRASG12C inhibitors (G12Ci) provided a major therapeutic advance, but resistance still limits their efficacy. To identify genes whose deletion augments efficacy of the...

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PMID: 37729426
DOI: 10.1158/0008-5472.CAN-23-2729
PMCID: PMC10841254

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