Combination of a SOS1-KRAS interaction inhibitor with a KRASG12C inhibitor combination can address intrinsic and acquired resistance leading to stronger and more durable response (RNA-Seq).

To investigate the transcriptomic changes associated with KRAS G12C inhibitor Adagrasib resistance and Adagrasib + SOS1 inhibitor (BI-3406) or Adagrasib + EGFR inhibitor (Cetuximab) combination treatment to overcome resistance. We performed differential gene expression analysis using RNA-seq generated from cell line derived xenograft (CDX) in vivo models. We compared different treatment conditions with DMSO treated condition. Overall design: CDX models were generated using NSCLC cell line NCI-H2122 and CRC cell line SW837. For each CDX category, expression data with DMSO treated and either single agent and combination treatment was generated.

为探究与KRAS G12C抑制剂阿达格拉西布（Adagrasib）耐药、以及联合使用阿达格拉西布与SOS1抑制剂BI-3406，或联合使用阿达格拉西布与EGFR抑制剂西妥昔单抗（Cetuximab）以克服耐药相关的转录组学变化，本研究采用源自细胞系的异种移植（CDX）体内模型的RNA测序数据开展差异基因表达分析，将不同处理组与二甲基亚砜（DMSO）处理组进行对照比较。总体实验设计：使用非小细胞肺癌（NSCLC）细胞系NCI-H2122与结直肠癌（CRC）细胞系SW837构建CDX模型；针对每一类CDX模型，分别获取二甲基亚砜处理组、单药处理组以及联合用药处理组的基因表达谱数据。