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KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
(NATURE PUBLISHING GROUP, 2019-06-13)
Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ...
Lipid-mRNA Nanoparticle Designed to Enhance Intracellular Delivery Mediated by Shock Waves.
(AMER CHEMICAL SOC, 2019-03-20)
Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs, e.g., recombinant protein, expression plasmids, or mRNA), which is a major barrier for clinical translation of macrodrug-based ...
Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds.
(NATL ACAD SCIENCES, 2019-02-12)
The RAS gene family is frequently mutated in human cancers, and the quest for compounds that bind to mutant RAS remains a major goal, as it also does for inhibitors of protein-protein interactions. We have refined ...
FGFR1 Expression and Role in Migration in Low and High Grade Pediatric Gliomas.
(Frontiers Media SA, 2019-03-13)
The heterogeneous and invasive nature of pediatric gliomas poses significant treatment challenges, highlighting the importance of identifying novel chemotherapeutic targets. Recently, recurrent Fibroblast growth factor ...
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma.
(NATURE RESEARCH, 2019-08-22)
Pediatric high-grade gliomas are among the deadliest of childhood cancers due to limited knowledge of early driving events in their gliomagenesis and the lack of effective therapies available. In this study, we investigate ...
Driving next-generation autophagy researchers towards translation (DRIVE), an international PhD training program on autophagy.
(TAYLOR & FRANCIS INC, 2019-02-01)
The European autophagy consortium Driving next-generation autophagy researchers towards translation (DRIVE) held its kick-off meeting in Groningen on the 14th and 15th of June 2018. This Marie Skłodowska-Curie Early Training ...
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
(NATURE PUBLISHING GROUP, 2019-03-07)
Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ...
RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2019-01-15)
PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic ...
Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models.
(SOC NUCLEAR MEDICINE INC, 2019-03-01)
In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR monoclonal ...
Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases.
(NATURE PUBLISHING GROUP, 2019-07-25)
Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on ...