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Targeting SRC in glioblastoma tumors and brain metastases: rationale and preclinical studies
Manmeet S Ahluwalia1, John de Groot, Wei Michael Liu
1Cleveland Clinic Main Campus, Cleveland, OH 44195, USA. ahluwam@ccf.org
Abstract:
Glioblastoma (GBM) is an extremely aggressive, infiltrative tumor with a poor prognosis. The regulatory approval of bevacizumab for recurrent GBM has confirmed that molecularly targeted agents have potential for GBM treatment. Preclinical data showing that SRC and SRC-family kinases (SFKs) mediate intracellular signaling pathways controlling key biologic/oncogenic processes provide a strong rationale for investigating SRC/SFK inhibitors, e.g., dasatinib, in GBM and clinical studies are underway. The activity of these agents against solid tumors suggests that they may also be useful in treating brain metastases. This article reviews the potential for using SRC/SFK inhibitors to treat GBM and brain metastases.
Insights
SRC/SFK inhibitors show promise for treating aggressive glioblastoma (GBM) and brain metastases. Clinical studies are investigating these targeted agents for improved outcomes in brain cancer patients.
Area of Science:
- Oncology
- Neuro-oncology
- Pharmacology
Background:
- Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options.
- Bevacizumab's approval for recurrent GBM highlights the potential of targeted therapies.
- SRC and SRC-family kinases (SFKs) are implicated in GBM's growth and spread.
Purpose of the Study:
- To review the potential of SRC/SFK inhibitors for treating glioblastoma.
- To explore the utility of SRC/SFK inhibitors in managing brain metastases.
Main Methods:
- Review of preclinical data on SRC/SFK signaling in GBM.
- Analysis of clinical studies investigating SRC/SFK inhibitors like dasatinib.
- Evaluation of SRC/SFK inhibitor activity in solid tumors and brain metastases.
Main Results:
- Preclinical data support SRC/SFK inhibitors' role in targeting key oncogenic pathways in GBM.
- SRC/SFK inhibitors demonstrate activity against solid tumors, suggesting potential for brain metastases.
Conclusions:
- SRC/SFK inhibitors represent a promising therapeutic strategy for glioblastoma.
- Targeting SRC/SFK pathways may offer new treatment avenues for brain metastases.
