MDB-41. Targeting PBK in Group 3 Medulloblastoma

BACKGROUND Group 3 medulloblastoma (MB) remains a challenging diagnosis especially due to a tendency for higher prevalence in infants and to develop frequent relapse. Targeted therapy remains elusive for these patients due to a lack of targetable alterations as well as poor understanding of driver mutations. PBK/TOPK has previously been identified as a hub gene in medulloblastoma and we have recently demonstrated that the LIN28B-PBK axis may be playing a crucial role in Group 3 MB development. METHODS Here we utilize transcriptomic profiling to identify pathways regulated by PBK in Group 3 MB to help identify potential vulnerabilities, immunofluorescence and cell viability analysis to calculate drug synergy. RESULTS Our analysis demonstrates that PBK knockdown leads to significant down regulation of cell cycle pathway genes. We also demonstrate that combining PBK inhibitor HI-TOPK-032 with the CDK 4/6 inhibitor palbociclib is synergistic in Group 3 MB cells. CONCLUSION Our investigations suggest PBK inhibition alone or in combination with other targeted agents may be a useful addition to existing therapy for these hard to treat cancers.