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. 2022 Feb 14;24(9):1438–1451. doi: 10.1093/neuonc/noac041

Fig. 1.

Fig. 1

High-grade pediatric CNS tumors upregulate ClpP, and imipridone-mediated ClpP hyperactivation reduces DMG cell viability. CPTAC/CBTTC datasets were quarried to assess ClpP expression across pediatric CNS cancers. (A) ClpP protein expression correlated with mRNA expression across pediatric brain tumors (P < .05). (B) ClpP mRNA and protein abundance significantly associated with tumor grade (P < .01). (C) ClpP protein is upregulated in HGG (P < .001), and M (P < .001) compared to LGG. HGG, High-grade glioma/astrocytoma; LGG, Low-grade glioma/astrocytoma; M, medulloblastoma. (D) ClpP RNA expression (highest 50% vs lowest 50%; RSEM TPM quantification) is significantly (p = 0.01) associated with lower overall survival in pediatric (4–14 years old) DMG patients (clinical data NCT02274987). (E, F) Human primary DMG cell viability is reduced in a dose-dependent manner following treatment with ONC201 (E) or ONC206 (F), summarized in Table (SD = Standard Deviation). (G) Dose-response treatment of DMG cells with ONC201-ONC206 combination reveled drug synergy (ZIP and Bliss score >10) or drug additivity (Loewe score –10 to 10).