Exploring the Anti-Tumor Activity and Mechanism of MYC Inhibitors (dSTR1180, dSTR112, dSTR116) in Neuroblastoma: In Vitro Profiling in BE2, Kelly, SH-SY5Y and Progression to Mouse Models
Session Number
2
Advisor(s)
Dr. Mark Applebaum, University of Chicago
Location
B116
Discipline
Medical and Health Sciences
Start Date
15-4-2026 11:10 AM
End Date
15-4-2026 11:55 AM
Abstract
Neuroblastoma is a common and aggressive cancer in young children, with survival rates below 50% in high-risk cases. Many aggressive tumors are driven by MYC family oncogenes, especially MYCN amplification, which promotes rapid tumor growth. Designed Synthetic Transcriptional Repressors (dSTR) are engineered molecules that mimic the MYC binding partner MAX and block MYC from activating genes involved in cancer cell growth. This study tested the effects of two MYC inhibitors, dSTR112 and dSTR1180, on neuroblastoma tumors. Initial in visensitive, showing reduced proliferation at low drug doses. In vivo experiments were conducted using athymic nude mice injected with Kelly cells. Mice received dSTR112 or dSTR1180 (10 or 20 mg/kg) on days 1, 3, 5, and 7, and tumor growth was monitored. Unexpectedly, tumors in both treatment groups grew faster than controls. To investigate this result, MYCN and MYCN target gene expression were analyzed using RNA sequencing, qPCR, and Western blot. RNA sequencing and qPCR showed no significant differences in MYCN expression compared to controls, while Western blot showed some MYCN upregulation in treated tumors. Although these results indicate the inhibitors did not suppress tumor growth under these conditions, they provide insight into MYCN driven tumor biology and support further investigation of dSTR compounds.tro testing identified the MYCN amplified Kelly neuroblastoma cell line as most
Exploring the Anti-Tumor Activity and Mechanism of MYC Inhibitors (dSTR1180, dSTR112, dSTR116) in Neuroblastoma: In Vitro Profiling in BE2, Kelly, SH-SY5Y and Progression to Mouse Models
B116
Neuroblastoma is a common and aggressive cancer in young children, with survival rates below 50% in high-risk cases. Many aggressive tumors are driven by MYC family oncogenes, especially MYCN amplification, which promotes rapid tumor growth. Designed Synthetic Transcriptional Repressors (dSTR) are engineered molecules that mimic the MYC binding partner MAX and block MYC from activating genes involved in cancer cell growth. This study tested the effects of two MYC inhibitors, dSTR112 and dSTR1180, on neuroblastoma tumors. Initial in visensitive, showing reduced proliferation at low drug doses. In vivo experiments were conducted using athymic nude mice injected with Kelly cells. Mice received dSTR112 or dSTR1180 (10 or 20 mg/kg) on days 1, 3, 5, and 7, and tumor growth was monitored. Unexpectedly, tumors in both treatment groups grew faster than controls. To investigate this result, MYCN and MYCN target gene expression were analyzed using RNA sequencing, qPCR, and Western blot. RNA sequencing and qPCR showed no significant differences in MYCN expression compared to controls, while Western blot showed some MYCN upregulation in treated tumors. Although these results indicate the inhibitors did not suppress tumor growth under these conditions, they provide insight into MYCN driven tumor biology and support further investigation of dSTR compounds.tro testing identified the MYCN amplified Kelly neuroblastoma cell line as most