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Updated: Apr 30, 2026
Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research
Published on: March 29, 2024
Re-evaluation of cytostatic therapies for meningiomas in vitro
Annette Wilisch-Neumann1, Doreen Pachow, Maren Wallesch
1Department of Neuropathology, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
Purpose:
The purpose was to re-evaluate in cell culture models the therapeutic usefulness of some discussed chemotherapies or targeted therapies for meningiomas with a special emphasis on the role of the neurofibromatosis type 2 (NF2) tumor suppressor, which had been neglected so far. In addition, the study intended to evaluate a potential benefit from a treatment with drugs which are well established in other fields of medicine and have been linked recently with tumor disease by epidemiological studies.
Methods:
Meningioma cell lines corresponding to various subtypes and pairs of syngenic meningioma cell lines with or without shRNA-induced NF2 knockdown were analyzed for their dose-dependent response to the drugs in microtiter tetrazolium assays, BrdU assays and for selected cases in ELISAs measuring nucleosome liberation to specifically separate cell death from pure inhibition of cell proliferation.
Results:
We confirmed a moderate efficacy of hydroxyurea (HU) in clinically relevant concentrations. Under appropriate dosing, we neither detected major responses to the alkylating compound temozolomide nor to various drugs targeting membrane receptors or enzymes (tamoxifen, erlotinib, mifepristone, losartan, metformin and verapamil). Only concentrations far beyond achievable serum levels generated significant effects with the exception of losartan, which showed no effects at all. Chemosensitivity varied markedly among meningioma cell lines. Importantly, cells with NF2 loss exhibited a significantly higher induction of cell death by HU.
Conclusions:
Alternative chemotherapeutic or targeted approaches besides HU have still to be evaluated in further studies, and the role of NF2 must be taken into account.
Insights
Hydroxyurea shows moderate efficacy for meningiomas, especially in NF2-deficient cells. Other tested therapies had limited effectiveness, highlighting the need for further research into meningioma treatments.
Area of Science:
- Oncology
- Genetics
Background:
- Meningiomas are primary brain tumors with limited treatment options.
- The role of the neurofibromatosis type 2 (NF2) tumor suppressor in meningioma therapy is under-explored.
Purpose of the Study:
- To re-evaluate chemotherapy and targeted therapy efficacy for meningiomas in cell culture.
- To investigate the impact of NF2 status on treatment response.
- To assess drugs with potential anti-cancer links from epidemiological studies.
Main Methods:
- Utilized various meningioma cell lines, including NF2-knockdown models.
- Assessed drug response using microtiter tetrazolium and BrdU assays.
- Measured nucleosome liberation to differentiate cell death from proliferation inhibition.
Main Results:
- Hydroxyurea (HU) demonstrated moderate efficacy at clinically relevant concentrations.
- Temozolomide, tamoxifen, erlotinib, mifepristone, losartan, metformin, and verapamil showed limited efficacy at achievable serum levels.
- NF2-deficient meningioma cells exhibited significantly enhanced cell death induction by HU.
Conclusions:
- Further investigation into alternative chemotherapeutic and targeted agents for meningiomas is warranted.
- The status of NF2 is a critical factor to consider in meningioma treatment strategies.
