AANS Neurosurgeon | Volume 26, Number 4, 2017

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Ludwig Researchers Identify Counterintuitive Approach to Treating a Brain Cancer

The loss of the tumor suppressor gene PTEN has been linked to tumor growth and chemotherapy resistance in the almost invariably lethal brain cancer glioblastoma multiforme (GBM). Now, Ludwig researchers have shown that one way to override the growth-promoting effects of PTEN deletion is, surprisingly, to inhibit a separate tumor suppressor gene. “It was an unexpected result because these are two verified tumor suppressor genes,” said study senior author Frank Furnari, a member of Ludwig Institute for Cancer Research, San Diego. The finding could lead to new therapies for treating a common sub-type of GBM and possibly other forms of cancer. “PTEN is one of the most frequently deleted tumor suppressor genes in cancer, so if we can take our finding to the next level and develop a therapeutic around it, it could have wide utility,” said Furnari, who is also a professor of Pathology at the University of California, San Diego. In their study, Furnari and his colleagues detail a previously unknown physical interaction between PTEN and DAXX. The latter is a so-called chaperone protein that helps guide the attachment of the protein H3.3 to compact looping fibers of DNA and its protein scaffolding, which are collectively called chromatin.

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