Article
Dissecting RAF Inhibitor Resistance by Structure-based Modeling Reveals Ways to Overcome Oncogenic RAS Signaling.
Cell systems - 22 Aug 2018
Rukhlenko Oleksii S, Khorsand Fahimeh, Krstic Aleksandar, Rozanc Jan, Alexopoulos Leonidas G, Rauch Nora, Erickson Keesha E, Hlavacek William S, Posner Richard G, Gómez-Coca Silvia, Rosta Edina, Fitzgibbon Cheree, Matallanas David, Rauch Jens, Kolch Walter, Kholodenko Boris N
Abstract excerpt
Clinically used RAF inhibitors are ineffective in RAS mutant tumors because they enhance homo- and heterodimerization of RAF kinases, leading to paradoxical activation of ERK signaling. Overcoming enhanced RAF dimerization and the resulting resistance is a challenge for drug design. Combining mul...
Topics
- Cell Line, Tumor
- Drug Resistance, Neoplasm
- Humans
- MAP Kinase Signaling System
- Molecular Docking Simulation
- Mutation
- Neoplasms
- Protein Kinase Inhibitors
- Protein Multimerization
- Signal Transduction