Northwestern University

“Predicting the Therapy Response of High-Grade Gliomas Based on a Network of Endogenous Modulators of Nuclear Factor-kappaB”

Temozolomide is a chemotherapeutic agent that is used as standard therapy in patients newly diagnosed with high-grade gliomas.  Predicting the tumor response to temozolomide and improving treatment efficacy remains a challenge.  Dr. Bredel theorizes that increased treatment success with this agent depends on a better understanding of the molecular mechanisms that lead to tumor resistance.

The focus of Dr. Bredel’s study is to addresse a complex cellular pathway [nuclear factor−κB (NF−κB)] and its associated endogenous (caused by factors within the cells) regulating network.  His previous work implicates this network in the resistance of high-grade gliomas to temozolomide therapy.  The project’s scope is to evaluate evidence that expression levels and status of several such endogenous modulators can be used to predict upfront the resistance and likely therapeutic outcome of high-grade glioma patients.

Currently, patients with relatively temozolomide-sensitive (versus temozolomide-resistant) tumors cannot be identified upfront with certainty on the basis of clinical or pathological characteristics. This work aims to consolidate evidence the lab previously obtained suggesting that molecular profiling of high-grade gliomas for these modulators may provide critical information as to the likelihood that the tumor will show a favorable or unfavorable response to temozolomide. Such profiles may not only impact therapeutic decision-making but may also provide new therapeutic leads to augment the treatment efficacy of temozolomide in high-grade gliomas using complementary targeted molecular approaches.

Dr. Bredel believes that this study holds the potential to form the basis for new therapeutic approaches to increase treatment efficacy and overcome the resistance of high-grade gliomas to temozolomide. He also hopes that resulting therapeutic approaches could potentially be implemented quickly into the clinical management of high-grade gliomas. 





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