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 multiple inhibitors could be more effective, but it is unclear how the best combinations can be chosen. We built a...
Read the complete abstract on PubMedTopics
Share this publication in a Topic to start or enrich a Post.