KRAS mutations occur in a quarter of all of human cancers, yet no selective drug has been approved to treat these tumors. Despite the recent development of drugs that block KRAS^G12C, the majority of KRAS oncoproteins remain undruggable. Here, we review recent efforts to validate individual components of the mitogen-activated protein kinase (MAPK) pathway as targets to treat KRAS-mutant cancers by comparing genetic information derived from experimental mouse models of KRAS-driven lung and pancreatic tumors with the outcome of selective MAPK inhibitors in clinical trials. We also review the potential of RAF1 as a key target to block KRAS-mutant cancers.

KRAS突变发生在所有人类癌症的四分之一中，但尚未批准选择性药物治疗这些肿瘤。尽管最近开发出了可阻断KRAS ^G12C的药物，但大多数KRAS癌蛋白仍不可滥用。在这里，我们通过比较从KRAS驱动的肺癌和胰腺肿瘤的实验小鼠模型获得的遗传信息与转归的结果进行比较，回顾了最近的工作，以验证有丝分裂原激活的蛋白激酶（MAPK）途径的各个成分作为治疗KRAS突变癌症的靶标。临床试验中的选择性MAPK抑制剂。我们还审查了RAF1作为阻断KRAS突变癌症的关键靶标的潜力。