Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencing in aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas. Single cell RNA sequencing (scRNAseq) of RBC-depleted cells from non-small cell lung tumor of 12 patients. ScRNAseq of lung tumors from KP model mice - 2 healthy samples, 2 tumor samples, 2 tumor PTC596 treated samples. *** The submitter states "Human raw data are not available for this Series due to patient privacy concerns." " [We] will not be submitting the raw human data to dbGap or EGA in this case." Thus, this submission is incomplete.