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Mary Ellen Hackett 

Manager, Communications Office

Email maryellen.hackett@nih.gov or call 301-401-8670 for all media related questions.

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Image showing KRAS OFF and KRAS ON inhibitors

Therapeutic strategies to overcome KRAS (OFF) inhibitors resistance

Understanding and overcoming resistance to KRAS G12C inhibitors remains a key focus in the fight against RAS-driven cancers. Experts describe non-genetic methods of resistance to G12C inhibitors that bind to the inactive, GDP-bound form of the protein, and propose the best therapeutic strategy.POSTED: 9/26/2024
New kid MAP2K4 sporting a pacifier, surrounded by tough guys

MAP2K4: New kid on the MAP Kinase block

Post-doc Robin A Jansen and her advisor Rene Bernards lay out a compelling argument for MAP2K4 inhibition as an effective combination therapy with RAS-targeted drugs.POSTED: 6/18/2024
A series of microscopic images show cells stained for E-cadherin (green) and Scribble (red) with DAPI (blue) labeling the nuclei. The images are presented in four columns: Control, 24 hours, 48 hours, and 48 hours Sotorasib followed by 48 hours drug-free. The changes in protein localization and cell morphology are visible over time and treatment conditions.

Inhibition of the MAPK pathway induces re-localization of membranous proteins, leading to adaptive resistance to KRAS G12C inhibitor mediated by YAP-induced MRAS

While promising and exciting, the new KRAS G12C inhibitors have been met with unknown mechanisms of resistance. Here, Yuta Adachi and Hiromichi Ebi describe their work uncovering a non-genetic resistance mechanism involving the mis-localization of scribble, which induces YAP-mediated MRAS expression and reactivates MAPK signaling.POSTED: 11/1/2023