Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Semin Oncol. 2021 Feb;48(1):10-18. doi: 10.1053/j.seminoncol.2021.02.003. Epub 2021 Feb 23.
Pancreatic cancer is a recalcitrant cancer with one of the lowest 5-year survival rates. A hallmark of pancreatic cancer is the prevalence of oncogenic mutation in the KRAS gene. The KRAS oncogene plays a critical role in the initiation and maintenance of pancreatic tumors and its signaling network represents a major target for therapeutic intervention. A number of inhibitors have been developed against kinase effectors in various Ras signaling pathways. Their clinical activity, however, has been disappointing thus far. More recently, covalent inhibitors targeting the KRAS oncoprotein have been developed. These inhibitors showed promising activity in KRAS mutant pancreatic cancer in early clinical trials. This review will present an updated summary of our understanding of mutant KRAS function in pancreatic cancer and discuss therapeutic strategies that target oncogenic KRAS signaling in this disease.
胰腺癌是一种难治性癌症，其 5 年生存率最低之一。胰腺癌的一个标志是 KRAS 基因中致癌突变的普遍存在。KRAS 癌基因在胰腺肿瘤的发生和维持中起着关键作用，其信号网络代表了治疗干预的主要靶点。已经开发了许多针对各种 Ras 信号通路中激酶效应物的抑制剂。然而，到目前为止，它们的临床活性令人失望。最近，针对 KRAS 癌蛋白的共价抑制剂已经被开发出来。这些抑制剂在早期临床试验中对 KRAS 突变型胰腺癌显示出了有希望的活性。这篇综述将对我们在胰腺癌中对突变型 KRAS 功能的理解进行更新总结，并讨论针对这种疾病致癌 KRAS 信号的治疗策略。
