Utilizing Omomyc to Target MYCN-Amplified Diffuse Intrinsic Pontine Gliomas

Genomic studies have shown that several types of pediatric brain tumors have dysregulation of MYC family members (c-MYC and MYCN). In fact, it has been estimated that about 50% of all human cancers have increased MYC, and this is correlated with tumor aggression and poor survival. Here we focus on targeting the MYCN oncogene in diffuse intrinsic pontine glioma (DIPG). DIPG has the worst prognosis of any pediatric brain tumor and is in desperate need of viable treatment options. Here we demonstrate that using a 90-amino acid peptide, termed “Omomyc” we are able to down-regulate endogenous MYCN and inhibit growth of MYCN overexpressing DIPG cells. Furthermore, Omomyc binds to promoter regions normally occupied by MYCN to affect transcription of a subset of genes including PLK1 and LDHA, among others. In vivo expression of Omomyc in DIPG cells implanted in mice slows disease progression, suggesting that MYCN targets are important for driving rapid tumor growth and may offer insight into potential targets for treatment of MYCN driven DIPGs. Overall design: RNASeq was performed on four different samples. Each sample was prepared as a singleton. Three samples are controls/references (1-SM-vumc-GFP_S1, 2-SM-vumc-GFP-dox_S2, 3-SM-vumc-omo_S3) and one sample is treated/test (4-SM-vumc-omo-dox_S4).