CDKN2A mutation + BRAF V600E

By using the novel PDX platform, the results presented in this study demonstrate that the treatments with Palbociclib or Dabrafenib/Trametinib significantly reduced tumor size. In conclusion, PDX models offer a deeper understanding of eGBM at the genomic level and facilitate the identification of potential therapeutic targets. Further translational studies of this novel PDX model hold promise for advancing the diagnosis and treatment of this specific subtype of glioblastoma.

Furthermore, ulixertinib treatment slowed tumor growth and significantly increased survival in NSG mice with orthotopic BT40 xenografts.Ulixertinib showed indications for anti-proliferative synergy in vitro, according to the Loewe and Bliss independence models, in combination with MEK inhibitors (trametinib, binimetinib) or senolytics (navitoclax, A1331852). Combinations with chemotherapy (carboplatin, vinblastine) were at most additive...The combination of ulixertinib with navitoclax was further investigated in the BT40 PDX mouse model, where tumor growth and survival were comparable to ulixertinib monotherapy.In conclusion, our data indicate a strong potential for ulixertinib as a clinically relevant therapeutic option for the treatment of pLGG to be further investigated in upcoming clinical trials. Potential synergism with MEK inhibitors and senolytics was noted and warrants further investigation.