Determination of the tumor microenvironment remodeling by KRAS targeted therapy in pancreatic cancer

Oncogenic KRAS is now recognized as a viable target for drug intervention; nevertheless, the efficacy of KRAS-targeted therapy is impeded by various resistance mechanisms. The intricate interplay between cancer cells and the cells within the tumor microenvironment (TME) actively contributes to the mutual promotion of resistance to KRAS-targeted therapies. To discern specific cell populations orchestrating tumor responses in pancreatic ductal adenocarcinoma (PDAC), we conducted single-cell RNA sequencing (scRNA-seq) on spontaneous tumors obtained from genetically engineered mouse models. This analysis was performed both before and after the inhibition or genetic ablation of KRAS, shedding light on the dynamic changes occurring at the single-cell level. Overall design: Spontaneous tumors from KPC or iKPC mice were dissected into single cells for library preparation.