학술논문

Sensitivity of human meningioma cells to the cyclin-dependent kinase inhibitor, TG02
Document Type
article
Source
Translational Oncology, Vol 13, Iss 12, Pp 100852- (2020)
Subject
Meningioma
TG02
Mutation
Methylation
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
1936-5233
Abstract
Standards of care for meningioma include surgical resection and radiotherapy whereas pharmacotherapy plays almost no role in this disease. 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). Four tumors assigned to the methylation class ben-2 showed the same class in culture whereas cultures from five non-ben-2 tumors showed a more malignant class in four patients. Cell cultures were uniformly sensitive to TG02 in the nanomolar range. Assignment of the cell cultures to a more malignant methylation class appeared to be more closely associated with TG02 sensitivity than assignment to a higher WHO grade of the primary tumors. Primary cell cultures from meningioma facilitate the investigation of the anti-meningioma activity of novel agents. TG02, an orally available cyclin-dependent kinase (CDK) inhibitor, warrants further exploration.