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Biological Chemistry

Blocking And Tackling Inoperable Brain Tumors

Cancer Research: Protein inhibitor prevents motor protein implicated in the formation of glioblastomas from taking off

by Judith Lavelle
September 14, 2015 | APPEARED IN VOLUME 93, ISSUE 36

Most adults don’t live much longer than a year after being diagnosed with glioblastoma, a type of cancer that spreads diffusely through brain tissue and is nearly impossible to surgically remove. Monica Venere of the Cleveland Clinic Foundation and colleagues have found that a motor protein called KIF11 helps drive the tumor’s deadly spread and that a known cancer drug has the power to stop it (Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed.aac6762). The researchers screened glioblastoma stem cells for known regulators of cell division and found that KIF11 is highly expressed. In healthy cells, KIF11 initially propels cells toward mitosis but is gradually degraded by a ubiquitin ligase during the rest of the cell cycle. For reasons the team is now investigating, glioblastoma stem cells don’t degrade KIF11, which leads to a quickly expanding, highly invasive tumor. The researchers administered the KIF11 inhibitor ispinesib—currently in clinical trials for other cancers—to mice with glioblastomas. The treated mice lived 36 days compared with untreated control mice that only survived for 24 days. “The tumors couldn’t take off until after we actually withdrew drug treatment,” Venere says. “It was a really dramatic shift in tumor latency.”

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