Gliobststoma (GBM) is a highly aggressive brain tumor that is resistant to many conventional cancer therapies. The kinase mTOR induces pathways that are aberrantly activated in GBM. However, mTOR inhibitors have not shown much promise for treating GBM. A new study in the Journal of Clinical Investigation indicates that mTOR inhibitor resistance in GBM is likely the result of compensatory glutamine metabolism. Kazuhiro Tanaka and colleagues at Kobe University determined that glutaminase and glutamine levels increase in GBM cells and xenografts in response to mTOR inhibition. Combined inhibition of glutatminase and mTOR suppressed growth of GBM tumor xenografts. Moreover, in patients with GBM, glutamine metabolism was increased in tumor tissue compared to noncancerous areas in the brain. Together, these results suggest that combined targeting of mTOR and glutamine metabolism should be further explored as a therapeutic strategy for GBM.
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TITLE: Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR-targeted therapies
AUTHOR CONTACT: Kazuhiro Tanaka
Kobe University Graduate School of Medicine, Kobe, , JPN
Phone: +81-78-382-5966; Fax: ; E-mail: kazutana@med.kobe-u.ac.jp
View this article at: http://www.jci.org/articles/view/78239?key=416518bc5068a2330378
Journal of Clinical Investigation