Background: Few options exist for the treatment of meningioma aside from surgery and radiation. There is a great need to find effective pharmacological therapies for meningiomas to treat patients who are not cured by surgery or radiation alone. In spite of the existence of hundreds of FDA-approved compounds, to date, no study has attempted to determine meningioma sensitivity to existing cancer therapy drugs in a large cohort of meningioma cell lines. Such a study could identify an already existing drug, or class of drugs, for the immediate treatment of meningiomas.
Methods: We created a high through put drug screen using a cell viability assay. We then screened the National Cancer Institute’s FDA approved cancer therapy drug library, consisting of 129 compounds, in six published meningioma cell lines, seven unpublished meningioma cell lines, and are continually screening expanded cells from patients’ tumors. Additionally, we are actively screening new tumors as they become available from our operating rooms. We used a single dose of drug at 1 µm concentration for the screen, and considered any compound that lowered cell viability by 50% at this dose to be positive hit for further investigation.
Results: Compounds targeting tyrosine kinase receptors, DNA synthesis, epigenetics, and DNA chelating drugs comprised the majority of the positive hits in the high throughput screen. Specifically, compounds targeting VEGF, ABL, ALK, FGFR, and PDGFR were frequent positive hits. Based on the cell lines we have screened thus far the most common compounds that inhibit meningioma growth are: ceritinib, dactinomycin, dasatinib, lenvatinib, nintedanib, ponatinib, SAHA, and carboplatin. Most of which have not been used to treat meningiomas. While these common pathways and compounds could allow for the broad treatment of meningiomas, it is important to note that many tumors showed enhanced sensitivity to unique compounds that were not efficacious in other cell lines. This also suggests that a screen of this type could be used to personalize medicine to base treatments on the sensitivity of the individual tumor.
Conclusion: We have developed a high through put assay that allows us to screen large libraries of compounds in meningioma cell lines and expanded cells from patient’s tumors. In screening 129 FDA approved cancer drugs, we have identified a small cohort of pharmacotherapies that have the potential to treat the majority of meningiomas. In addition to identifying compounds for the broad treatment of meningiomas, our system allows us to rapidly screen tumors for drug sensitivity to generate a sensitivity profile for each individual patient, and could lead to the development of truly personalized medicine.
