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This Week in Cancer Discovery: May 18, 2012

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In Cancer Discovery this week, a team of US researchers reports on the different sensitivities of glioma-specific versus lung-cancer specific EGFR mutations to EGFR inhibitors. Activation of EGFR in glioblastoma occurs through mutations in the extracellular domain, and such glioblastomas usually respond poorly to the EGFR inhibitor erlotinib, unlike lung cancers with kinase-domain EGFR mutations, the authors write. For this study the team used RNA interference to show that glioblastoma cells carrying EGFR extracellular mutations display "EGFR addiction." In contrast to kinase-domain-mutant lung cancers, "glioma-specific EGFR [extracellular-domain] mutants are poorly inhibited by EGFR inhibitors that target the active kinase conformation (e.g., erlotinib)," the team adds. "Inhibitors that bind to the inactive EGFR conformation, however, potently inhibit EGFR [extracellular-domain] mutants and induce cell death in EGFR-mutant [glioblastoma] cells."

Also in Cancer Discovery this week, researchers in France report blocking the late mobilization of circulating endothelial progenitor cells in order to reverse a tumor's resistance to vascular-disrupting agents. When the team administered these agents to tumor-bearing mice, they observed an early efflux of circulating endothelial progenitor cells followed by a later tumor-specific "burst" of these cells. However, when the researchers combined the vascular-disrupting agents with antiangiogenic drugs, "[they] could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst might be crucial to tumor recovery after VDA therapy."

The Scan

Team Tracks Down Potential Blood Plasma Markers Linked to Heart Failure in Atrial Fibrillation Patients

Researchers in BMC Genomics found 10 differentially expressed proteins or metabolites that marked atrial fibrillation with heart failure cases.

Study Points to Synonymous Mutation Effects on E. Coli Enzyme Activity

Researchers in Nature Chemistry saw signs of enzyme activity shifts in the presence of synonymous mutations in a multiscale modeling analysis of three Escherichia coli genes.

Team Outlines Paternal Sample-Free Single-Gene Approach for Non-Invasive Prenatal Screening

With data for nearly 9,200 pregnant individuals, researchers in Genetics in Medicine demonstrate the feasibility of their carrier screening and reflex single-gene non-invasive prenatal screening approach.

Germline-Targeting HIV Vaccine Shows Promise in Phase I Trial

A National Institutes of Health-led team reports in Science that a broadly neutralizing antibody HIV vaccine induced bnAb precursors in 97 percent of those given the vaccine.