Marco Wallroth

TL;DR: A large-scale RNAi screen is conducted in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features.

TL;DR: It is shown that activation of RAF(WT) is ATP dependent and directly linked to RAF kinase activity, which supports a mechanism involving inhibitory autophosphorylation of RAF's phosphate-binding loop that, when disrupted either through pharmacologic or genetic alterations, results inactivation of RAF and the mitogen-activated protein kinase (MAPK) pathway.

TL;DR: The utility of an in vitro to in vivo workflow utilizing immunoprecipitation and mass spectrometry to map phosphorylation sites on endogenous kinase substrates is demonstrated and can be readily generalized to identify target modulation read‐outs for other potential kinase cancer targets.

TL;DR: It is shown that combining a MEK inhibitor with a Raf compound causes inhibition of both pERK and cell growth and may therefore have significant advantages in the clinic, and is suggested a model in which compound binding to one Raf molecule induces dimerization and conformational activation of a partner Raf molecule in the dimer.