OS8.6 Sensitivity of human meningioma cells to the cyclin-dependent kinase inhibitor, TG02. (6th September 2019)

• Record Type: Journal Article
• Authors: Le Rhun, E; von Achenbach, C; Sahm, F; Wang, S S; Neidert, M C; Rushing, E; Lawhon, T; Schneider, H; von Deimling, A; Weller, M
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 3
• Page Start: iii17
• Page End: iii17
• Publication Date: 2019-09-06
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz126.056
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Standards of care for meningioma include surgical resection, which may be curative, and radiotherapy as required. Pharmacotherapy plays only a minor role in this disease; however, novel systemic approaches are urgently needed for patients who are no longer candidates for local therapy. MATERIAL AND METHODS: We generated primary cultures from surgically removed meningiomas to explore the activity of a novel cyclin-dependent kinase inhibitor, TG02, in meningioma cell cultures. Tumor and cell cultures were characterized by mutation profiling and DNA methylation profiling. DNA methylation data were used to allot each sample to one out of six previously established meningioma methylation classes: benign ( ben )-1, 2, 3, intermediate ( int )-A, B, and malignant ( mal ). The activity of TG02 was assessed by standard cell culture assays. RESULTS: Cell cultures were derived from nine meningiomas. Four tumors assigned to the methylation class ben-2 showed the same class in the cell culture whereas cell cultures from five non- ben-2 tumors showed a different class, a more malignant class in four of five patients. Cell cultures were uniformly sensitive to the growth inhibitory effects of TG02 in the nanomolar range. Assignment of the cell cultures to a more malignant methylation classifier appeared to be more closely associated with TG02 sensitivity than assignment to a higher WHO grade of the primary tumors. CONCLUSION: Primary cell cultures from meningioma facilitate the investigation of the anti-meningioma activity of novel agents. TG02, an orally available cyclin-dependent kinase inhibitor, warrants further exploration in this disease.