CDKs as target structures for cancer therapy – an in vitro analysis on patient-derived glioblastoma cell lines

Background Glioblastoma (GBM) is the most common and lethal brain tumor. Despite radical therapy consisting of surgical resection, combined chemoradiotherapy and continuous development of treatment strategies survival prognosis remains poor. This underlines the urgent need for new (alternative) therapeutic strategies. Cyclin-dependent kinases (CDKs) play essential roles in regulation of cell cycle progression, transcription, DNA damage repair, stem cell self-renewal as well as nerve cell differentiation. Glioma cells frequently show genomic alterations involved in cell cycle control, especially in specific interphase CDKs essential for tumor cell proliferation. To counteract the CDK dysregulation in malignant patient-derived glioma cell cultures we used selective CDK inhibitors (CDKIs) like abemaciclib (AB), palbociclib (P) and the novel inhibitor dinaciclib (D). Since GBM are also known to be highly radioresistant we tested these inhibitors in combination with radiation therapy (RT).