Narrowing the focus: a toolkit to systematically connect oncogenic signaling pathways with cancer phenotypes

Abstract

Functional genomics approaches such as gain- and loss-of-function screening can efficiently reveal genes that control cancer cell growth, survival, signal transduction, and drug resistance, but distilling the results of large-scale screens into actionable therapeutic strategies is challenging given our incomplete understanding of the functions of many genes. Research over several decades, including the results of large-scale cancer sequencing projects, has made it clear that many oncogenic properties are controlled by a common set of core oncogenic signaling pathways. By directly screening this core set of pathways, rather than much larger numbers of individual genes, it may be possible to more directly and efficiently connect functional genomic screening results with therapeutic targets. Here, we describe the recent development of methods to directly screen oncogenic pathways in high-throughput. We summarize the results of studies that have used pathway-centric screening to map the pathways of resistance to targeted therapies in diverse cancer types, then conclude by expanding on potential future applications of this approach.

A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent

“…Lentiviral supernatants and plasmids encoding wild-type and L240F mutant TUBB were obtained from Jonathan Weissman (Jost et al, 2017) and co-transfected with packaging plasmids (Singleton and Wood, 2016) using Lipofectamine 2000 (Thermo Fisher Scientific) into HEK293T cells to generate recombinant lentiviruses. Viral supernatant was harvested 48 and 72 hr post-transfection and filtered prior to further use.…”

Predatory journals: how their publishers operate and how to avoid them

“…Prvním je podezřele rychlé peer review, když např. v červenci a září roku 2016 byly v časopise publikovány články s recenzním řízením trvajícím pouze 2-3 dny [19,20]. Druhým je lživé tvrzení na úvodní stránce časopisu (http://www.…”