Simultaneous Targeting of KRAS and CDK4 Synergistically Induces Durable Growth Arrest in Pancreatic Cancer Cells [AsPC-1_RNA_Seq]

We show that the KRAS-G12D inhibitor MRTX1133 synergizes with the CDK4/6 inhibitor Palbociclib to eliminate pancreatic ductal adenocarcinoma (PDAC) cells (AsPC-1) harboring KRAS-G12D mutations. This synergy was especially pronounced following drug washout, indicating a durable cellular response. Mechanistically, the combinations induced sustained cell cycle arrest. Overall design: RNA-Sequencing of AsPC-1 cells treated for 24 h with DMSO, Palbociclib (5 µM), MRTX1133 (0.5 µM) or the combination.

本研究证实，KRAS-G12D抑制剂MRTX1133与CDK4/6抑制剂帕博西尼 (Palbociclib) 可协同清除携带KRAS-G12D突变的胰腺导管腺癌 (pancreatic ductal adenocarcinoma, PDAC) AsPC-1细胞。该协同效应在药物洗脱后尤为显著，提示存在持久的细胞应答反应。从机制层面而言，联合用药可诱导持续的细胞周期阻滞。实验整体设计：对经二甲基亚砜 (DMSO)、帕博西尼 (5 μM)、MRTX1133 (0.5 μM) 或联合用药处理24小时的AsPC-1细胞进行RNA测序 (RNA-Sequencing)。