Combination of Ribociclib and Gemcitabine for the Treatment of Medulloblastoma

Abstract

Group3 (G3) medulloblastoma (MB) is one of the deadliest gemcitabine was well tolerated, slowed tumor progression and forms of the disease for which novel treatment is desperately metastatic spread, and increased survival. Expression-based gene needed. Here we evaluate ribociclib, a highly selective CDK4/6 activity and cell state analysis investigated the effects of the inhibitor, with gemcitabine in mouse and human G3MBs. Ribocombination after short- and long-term treatments. Molecular ciclib central nervous system (CNS) penetration was assessed by analysis of treated versus untreated tumors showed a significant in vivo microdialysis and by IHC and gene expression studies and decrease in the activity and expression of genes involved in cell-found to be CNS-penetrant. Tumors from mice treated with cycle progression and DNA damage response, and an increase short term oral ribociclib displayed inhibited RB phosphorylain the activity and expression of genes implicated in neuronal tion, downregulated E2F target genes, and decreased proliferaidentity and neuronal differentiation. Our findings in both tion. Survival studies to determine the efficacy of ribociclib and mouse and human patient-derived orthotopic xenograft models gemcitabine combination were performed on mice intracranially suggest that ribociclib and gemcitabine combination therapy implanted with luciferase-labeled mouse and human G3MBs. warrants further investigation as a treatment strategy for children Treatment of mice with the combination of ribociclib and with G3MB.