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Targeted and Personalized Therapy for Difficult Benign Brain Tumors: A Review
Polina Chliapnikov1, Mark Bernstein1
1Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada.
Background:
Difficult benign intracranial tumors (including meningiomas, schwannomas, neurofibromatosis-related tumors, and pituitary neuroendocrine tumors) have substantial morbidity in patients. Due to their limited treatment options, there is a need for individualized treatment beyond histological and surgical approaches.
Objective:
To summarize how novel treatment innovations have been implemented for these tumors, meningiomas and schwannomas are prioritized, followed by NF-associated neoplasms, and then pituitary neuroendocrine tumors in comparison to low-grade gliomas.
Methods:
We summarize the current knowledge relating to targeted therapies for gliomas, meningiomas, schwannomas, neurofibromatosis (NF) tumors, and pituitary neuroendocrine tumors to investigate an individual's treatment options for difficult benign brain tumors. This review synthesizes evidence on tumor genomics and molecular markers, supported by methylation-based classification, immunohistochemistry, and functional assays, emphasizing current clinical applications.
Evidence Synthesis:
The recent data show that DNA methylation-based models can predict post-surgical outcomes and radiotherapy responses, enabling risk stratification and radiotherapy benefit prediction. Early signals support target-directed treatment, including cMET blockade that radiosensitizes NF2 schwannoma models, brigatinib-associated tumor shrinkage in NF2-deficient models, and PitNET organoid data.
Conclusions:
We support clinical decision-making that utilizes molecular profiling with functional testing to guide targeted treatment. We also identify evidence gaps such as biomarker-defined prospective trials that are needed for broader clinical implementation.
Insights
Individualized treatment for difficult benign brain tumors is advancing with molecular profiling. Novel targeted therapies show promise for meningiomas, schwannomas, and neuroendocrine tumors, guiding clinical decisions.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Genomics
Background:
- Difficult benign intracranial tumors like meningiomas and schwannomas cause significant patient morbidity.
- Limited treatment options necessitate individualized approaches beyond traditional surgery and histology.
Purpose of the Study:
- To review novel treatment innovations for difficult benign brain tumors.
- Prioritize meningiomas, schwannomas, neurofibromatosis-associated neoplasms, and pituitary neuroendocrine tumors.
- Compare treatment strategies with low-grade gliomas.
Main Methods:
- Synthesized current knowledge on targeted therapies for various brain tumors.
- Reviewed tumor genomics and molecular markers.
- Incorporated methylation-based classification, immunohistochemistry, and functional assays.
Main Results:
- DNA methylation models predict post-surgical outcomes and radiotherapy response for risk stratification.
- Early evidence supports targeted treatments like cMET blockade and brigatinib in preclinical models.
- Pituitary neuroendocrine tumor organoid data shows therapeutic potential.
Conclusions:
- Molecular profiling and functional testing should guide targeted treatment decisions.
- Evidence gaps exist, particularly in biomarker-defined prospective trials for clinical implementation.
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