ArticleNeuro-oncology2021
Evaluation of a procaspase-3 activator with hydroxyurea or temozolomide against high-grade meningioma in cell culture and canine cancer patients.
Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Recurrent meningioma treated with boron neutron capture therapy: a feasibility study with dosimetric and clinical correlates.Journal of neuro-oncology · 2025Article
- Possible involvement of cerebrospinal fluid drop metastasis in the survival of French bulldogs after radiotherapy for presumed glial brain tumors.Open veterinary journal · 2025Article
- PAC-1 Synergizes with Sunitinib to Enhance Cell Death in Pancreatic Neuroendocrine Tumors.ACS pharmacology & translational science · 2025Article
- Raptinal: a powerful tool for rapid induction of apoptotic cell death.Cell death discovery · 2024Review
- Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.British journal of cancer · 2023Article
- Target-Agnostic P-Glycoprotein Assessment Yields Strategies to Evade Efflux, Leading to a BRAF Inhibitor with Intracranial Efficacy.Journal of the American Chemical Society · 2022Article
- Phase I dose-escalation study of procaspase-activating compound-1 in combination with temozolomide in patients with recurrent high-grade astrocytomas.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundHigh-grade meningioma is an aggressive type of brain cancer that is often recalcitrant to surgery and radiotherapy, leading to poor overall survival. Currently, there are no FDA-approved drugs for meningioma, highlighting the need for new therapeutic options, but development is challenging due to the lack of predictive preclinical models.
methodsTo leverage the known overexpression of procaspase-3 in meningioma, PAC-1, a blood-brain barrier penetrant procaspase-3 activator, was evaluated for its ability to induce apoptosis in meningioma cells. To enhance the effects of PAC-1, combinations with either hydroxyurea or temozolomide were explored in cell culture. Both combinations were further investigated in small groups of canine meningioma patients and assessed by MRI, and the novel apoptosis tracer, [18F]C-SNAT4, was evaluated in patients treated with PAC-1 + HU.
resultsIn meningioma cell lines in culture, PAC-1 + HU are synergistic while PAC-1 + TMZ show additive-to-synergistic effects. In canine meningioma patients, PAC-1 + HU led to stabilization of disease and no change in apoptosis within the tumor, whereas PAC-1 + TMZ reduced tumor burden in all three canine patients treated.
conclusionsOur results suggest PAC-1 + TMZ as a potentially efficacious combination for the treatment of human meningioma, and also demonstrate the utility of including pet dogs with meningioma as a means to assess anticancer strategies for this common brain tumor.
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