Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Cancer Cell. 2020 Apr 13;37(4):543-550. doi: 10.1016/j.ccell.2020.03.013.
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, 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，但尚无专门用于治疗这些肿瘤的选择性药物获得批准。尽管最近开发了可阻断 KRAS 的药物，但大多数 KRAS 癌蛋白仍然不可用药。在这里，我们通过将源自 KRAS 驱动的肺和胰腺肿瘤实验小鼠模型的遗传信息与临床前试验中选择性 MAPK 抑制剂的结果进行比较，来回顾最近验证丝裂原活化蛋白激酶（MAPK）途径的各个成分作为治疗 KRAS 突变型癌症的靶点的努力。我们还回顾了 RAF1 作为阻断 KRAS 突变型癌症的关键靶标的潜力。
