Targeting the KRAS α4-α5 allosteric interface inhibits pancreatic cancer tumorigenesis.

ABSTRACT: RAS is the most frequently mutated oncogene in human cancer with nearly ~20% of cancer patients possessing mutations in one of three RAS genes (K, N or HRAS). However, KRAS is mutated in nearly 90% of pancreatic ductal carcinomas (PDAC). Although pharmacological inhibition of RAS has been challenging, KRAS(G12C)-specific inhibitors have recently entered the clinic. While KRAS(G12C) is frequently expressed in lung cancers, it is rare in PDAC. Thus, more broadly efficacious RAS inhibitors are needed for treating KRAS mutant-driven cancers such as PDAC. A RAS-specific tool biologic, NS1 Monobody, inhibits HRAS- and KRAS-mediated signalling and oncogenic transformation both in vitro and in vivo by targeting the α4-α5 allosteric site of RAS and b

SUBMITTER: Khan I 

PROVIDER: S-EPMC9707541 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature