Suman Mukhopadhyay, Hsin-Yi Huang, Ziyan Lin, Michela Ranieri, Shuai Li, Soumyadip Sahu, Yingzhuo Liu, Yi Ban, Kayla Guidry, Hai Hu, Alfonso Lopez, Fiona Sherman, Yi Jer Tan, Yeuan Ting Lee, Amanda P Armstrong, Igor Dolgalev, Priyanka Sahu, Tinghu Zhang, Wenchao Lu, Nathanael S Gray, James G Christensen, Tracy T Tang, Vamsidhar Velcheti, Alireza Khodadadi-Jamayran, Kwok-Kin Wong, Benjamin G Neel
UNLABELLED: 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 G12Cis adagrasib (MRTX-849) or adagrasib plus TNO155 (SHP2i), we performed genome-wide CRISPR/Cas9 screens on KRAS/STK11-mutant NSCLC lines...
December 15, 2023: Cancer Research