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Updated: Jun 8, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Novel targeted agents for platelet-derived growth factor receptor and c-KIT in malignant gliomas
Patrick G Morris1, Lauren E Abrey
1Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. morrisp1@mskcc.org
Abstract:
Malignant gliomas are a heterogeneous group of tumors with a varying natural history and response to treatment. Despite current therapeutic strategies, these tumors almost universally recur after excision and are associated with a poor survival. Increasingly, the true heterogeneity of these tumors is being correlated with distinct molecular subgroups. Platelet-derived growth factor receptor (PDGFR) alpha is almost universally expressed on glioma cells; expression of the proto-oncogene c-KIT has also been reported. These findings have led to the clinical investigation of inhibitors of this pathway, such as imatinib and dasatinib, for the treatment of recurrent malignant glioma. To date, this approach in unselected patients has been disappointing. However, isolated responses have been seen, which may correlate with constitutive activation of one or more of the corresponding tyrosine kinases. In the future, it is hoped that an increasing knowledge of glioma biology will translate into the more judicious use of these and other targeted therapies, resulting in improvements in patient outcomes. This review describes the preclinical science behind PDGFR and c-KIT, the clinical importance of these molecular pathways and the available data from translational clinical trials.
Insights
Targeted therapies like imatinib show limited success for malignant gliomas. Future treatments may improve outcomes by better understanding PDGFR and c-KIT pathways in specific molecular subgroups.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Translational Medicine
Background:
- Malignant gliomas are aggressive brain tumors with poor prognoses.
- Tumor recurrence is nearly universal despite current treatments.
- Glioma heterogeneity is increasingly linked to distinct molecular subgroups.
Purpose of the Study:
- To review the preclinical science of Platelet-Derived Growth Factor Receptor (PDGFR) and c-KIT pathways.
- To discuss the clinical significance of these molecular pathways in glioma.
- To analyze data from translational clinical trials investigating PDGFR and c-KIT inhibitors.
Main Methods:
- Review of preclinical studies on PDGFR and c-KIT.
- Analysis of clinical trial data for targeted therapies in malignant glioma.
- Correlation of molecular subgroups with treatment response.
Main Results:
- PDGFR-alpha and c-KIT are expressed in glioma cells.
- Targeted inhibitors (imatinib, dasatinib) have shown disappointing results in unselected patients.
- Isolated responses suggest potential efficacy in specific molecular contexts with activated tyrosine kinases.
Conclusions:
- Current targeted therapies for malignant glioma are limited in unselected populations.
- Understanding glioma biology and molecular subgroups is crucial for effective treatment.
- Future research aims to translate molecular insights into improved patient outcomes with targeted therapies.
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