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."