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. Spontaneous tumors from KPC or iKPC mice were dissected into single cells for library preparation.

致癌性KRAS（Oncogenic KRAS）现已被公认为药物干预的可行靶点；然而，KRAS靶向治疗的疗效却受到多种耐药机制的阻碍。癌细胞与肿瘤微环境（tumor microenvironment，TME）内的细胞之间存在复杂的相互作用，这种作用积极推动了KRAS靶向治疗耐药性的共同形成。为明确胰腺导管腺癌（Pancreatic Ductal Adenocarcinoma，PDAC）中调控肿瘤应答的特定细胞群，我们对从基因工程小鼠模型中获取的自发性肿瘤开展了单细胞RNA测序（Single-Cell RNA Sequencing，scRNA-seq）分析。该分析分别在KRAS抑制或基因敲除前后进行，为阐明单细胞层面的动态变化提供了重要线索。研究人员从KPC小鼠与iKPC小鼠中获取自发性肿瘤，将其解离为单个细胞以完成文库制备。