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Updated: May 28, 2026
Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing
Published on: June 9, 2016
Will kinase inhibitors make it as glioblastoma drugs?
Ingo K Mellinghoff1, Nikolaus Schultz, Paul S Mischel
1Department and Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. mellingi@mskcc.org
Abstract:
Kinase inhibitors have emerged as effective cancer therapeutics in a variety of human cancers. Glioblastoma (GBM), the most common malignant brain tumor in adults, represents a compelling disease for kinase inhibitor therapy because the majority of these tumors harbor genetic alterations that result in aberrant activation of growth factor signaling pathways. Attempts to target the Ras-Phosphatidylinositol 3-kinase (PI3K)-mammalian Target of Rapamycin (mTOR) axis in GBM with first generation receptor tyrosine kinase (RTK) inhibitors and rapalogs have been disappointing. However, there is reason for renewed optimism given the now very detailed knowledge of the cancer genome in GBM and a wealth of novel compounds entering the clinic, including next generation RTK inhibitors, class I PI3K inhibitors, mTOR kinase inhibitors (TORKinibs), and dual PI3(K)/mTOR inhibitors. This chapter reviews common genetic alterations in growth factor signaling pathways in GBM, their validation as therapeutic targets in this disease, and strategies for future clinical development of kinase inhibitors for high grade glioma.
Insights
Kinase inhibitors show promise for treating glioblastoma (GBM) by targeting aberrant growth pathways. Novel therapies offer renewed optimism for effective GBM treatment, despite earlier challenges.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Glioblastoma (GBM) is a common adult brain tumor with activated growth factor signaling.
- First-generation kinase inhibitors targeting the Ras-PI3K-mTOR axis in GBM have shown limited success.
- Detailed cancer genome knowledge and novel inhibitors offer new therapeutic avenues.
Purpose of the Study:
- To review genetic alterations in GBM growth factor pathways.
- To discuss the therapeutic validation of these targets in GBM.
- To outline strategies for developing future kinase inhibitors for high-grade glioma.
Main Methods:
- Review of genetic alterations in GBM growth factor signaling pathways.
- Analysis of therapeutic target validation in GBM.
- Examination of clinical development strategies for novel kinase inhibitors.
Main Results:
- Common genetic alterations in GBM activate growth factor signaling pathways.
- Previous attempts with first-generation inhibitors and rapalogs were disappointing.
- Next-generation RTK inhibitors, PI3K inhibitors, TORKinibs, and dual PI3(K)/mTOR inhibitors are emerging.
Conclusions:
- Despite past challenges, novel kinase inhibitors present renewed optimism for GBM treatment.
- Targeting specific genetic alterations in GBM pathways is crucial for therapeutic success.
- Future clinical development should focus on advanced kinase inhibitor strategies for high-grade glioma.
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