Discovery of combination therapy for KRAS mutant cancer

背景靶向治疗剂，包括MEK和ERK激酶抑制剂，对KRAS突变的实体瘤的疗效非常有限。可以协同杀死KRAS突变癌细胞的药物组合的鉴定可能导致新的治疗方式。目的.在这个项目中，我们的目标是进行高通量药物组合筛选，以确定在体外KRAS突变癌细胞中显示出强选择性的协同组合。我们的目标是验证筛选结果并评估其翻译潜力。成就。我们已经完成了初步筛选，并确定了在KRAS突变癌细胞系中具有协同细胞杀伤作用的候选药物组合。我们目前正在研究这些组合的机制。

BACKGROUND. Targeted therapeutic agents, including MEK and ERK kinase inhibitors, haves shown very limited efficacy against solid tumors with KRAS mutations. The identification of drug combinations that can synergistically kill KRAS mutant cancer cells could lead to new therapeutic modality. PURPOSE. In this project we aim to carry out a high-throughput drug combination screen to identify synergistic combinations that show strong selectivity in KRAS mutant cancer cells in vitro. We aim to validate hits from the screen and evaluate their translational potential. ACCOMPLISHMENT. We have completed the primary screen and have identified candidate drug combinations with synergistic cell killing effect in KRAS mutant cancer cell lines. We are currently investigating the mechanisms of these combinations.