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Mouse study finds adding γ-secretase inhibitor to chemo can suppress tumor recurrence

-- Jeff Muise

Wednesday, August 25, 2010 (Last Updated: 08/26/2010)

WEDNESDAY, Aug. 25 (HealthDay News) -- For glioblastoma multiforme, the most common and aggressive type of brain tumor, treatment with the chemotherapy agent temozolomide (TMZ) plus a γ-secretase inhibitor (GSI) to suppress tumor recurrence offers a novel and promising therapeutic approach, according to a study in mice published online Aug. 24 in Cancer Research.

Candace A. Gilbert, of the University of Massachusetts Medical School in Worcester, and colleagues treated cultured glioma cells with TMZ and added GSIs to suppress Notch signaling activity. The treated cells were injected into immunodeficient mice, which were then monitored for tumor formation. In another group of mice, untreated cells were injected, and then the mice were treated and monitored.

The researchers found that adding GSI to TMZ treatment decreased tumor recurrence by suppressing the Notch pathway, but the effect was only achieved if the GSI was administered after the TMZ, not before or simultaneously. In the immunodeficient mice which had received cells pretreated with TMZ and GSI, tumor latency and survival were extended. In the mice that received untreated cells and developed tumors, TMZ and GSI treatment blocked tumor progression in half of the mice.

"These data show the importance of the Notch pathway in chemoprotection and repopulation of TMZ-treated gliomas. The addition of GSIs to current treatments is a promising approach to decrease brain tumor recurrence," the authors write.

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Specialties Hematology & Oncology

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