Hoa Nguyen

TL;DR: The structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity, and a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily are described, demonstrating that BRAF-mutant melanomas are highly dependent on B- RAF kinases activity.

TL;DR: PLX4720, a 7-azaindole derivative that inhibits B-RafV600E with an IC50 of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays and represents the entire discovery process from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B- RafV 600E-driven tumors.

TL;DR: Surprisingly, extensive treatment results in elimination of ∼99% of all microglia brain-wide, showing that microglian homeostasis in the adult brain are physiologically dependent upon CSF1R signaling.

TL;DR: In this article, the authors performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib.

TL;DR: These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.