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

Imran Khan, Catherine MarElia-Bennet, Julia Lefler, Mariyam Zuberi, Eric Denbaum, Akiko Koide, Dean M. Connor, Ann-Marie Broome, Thierry Pécot, Cynthia Timmers, Michael C. Ostrowski, Shohei Koide & John P. O’Bryan
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...
1 citation reported since publication in 2021.
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