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Updated: Jun 4, 2026
Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
Signal transduction inhibitors and antiangiogenic therapies for malignant glioma
Ingo K Mellinghoff1, Andrew B Lassman, Patrick Y Wen
1Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USA. mellingi@mskcc.org
Abstract:
Detailed characterization of the cancer genome in a large number of primary human glioblastomas has identified recurrent alterations that result in deregulation of signal transduction pathways and are "druggable" with a growing number of small molecule pharmaceuticals. While many of these compounds have shown clinical activity in other human cancers harboring similar genetic alterations, the clinical experience in glioblastoma has been disappointing thus far with only rare and transient radiographic responses. Our understanding of drug resistance is confounded by the uncertainty of drug delivery across the blood brain barrier and the limited knowledge to what extent the growth of these tumors depends on any particular signaling pathway. This uncertainty is, at least in part, due to shortcomings in the current approach to evaluate signal transduction inhibitors in glioma patients, including drug testing in molecularly unselected patient populations, limited documentation of drug penetration and target inhibition in tumor tissue, and use of radiographic response criteria that may not be optimal for the evaluation of these compounds. © 2011 Wiley-Liss, Inc.
Insights
Glioblastoma cancer genome research reveals druggable targets, but clinical trials show limited success due to drug delivery and resistance challenges. New evaluation methods are needed for targeted glioblastoma therapies.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Glioblastoma harbors recurrent genetic alterations activating signal transduction pathways.
- Small molecule pharmaceuticals targeting these pathways show promise in other cancers.
Purpose of the Study:
- To address the disappointing clinical outcomes of targeted therapies in glioblastoma.
- To identify shortcomings in current evaluation methods for signal transduction inhibitors in glioma patients.
Main Methods:
- Characterization of the cancer genome in primary human glioblastomas.
- Review of clinical trial data for targeted therapies in glioblastoma.
- Analysis of factors confounding drug resistance, including blood-brain barrier penetration.
Main Results:
- Recurrent genetic alterations leading to deregulated pathways are identified as "druggable" targets.
- Clinical trials in glioblastoma have yielded rare and transient radiographic responses.
- Uncertainty in drug delivery, target inhibition, and optimal response criteria complicates evaluation.
Conclusions:
- Current approaches to evaluating signal transduction inhibitors in glioblastoma are suboptimal.
- Improved methods are needed to assess drug penetration, target engagement, and clinical efficacy.
- Addressing drug delivery and resistance mechanisms is crucial for advancing glioblastoma treatment.
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