An Integrative Drug-Induced Transcriptomic Analysis Identifies Novel MYC Antagonists and Potential Synergistic Drug Combinations.

ABSTRACT: MYC is among the most frequently dysregulated oncogenes in human cancer, yet its direct targeting remains a significant challenge. Here, we present an in-silico integrative screening approach to identify compounds and combinations that can block MYC's oncogenic function by specifically disrupting its transcriptional regulatory function. Using a doxycycline (DOX)-inducible model, we established a MYC loss-of-function (LOF) gene signature that specifically captures the molecular consequences corresponding to the loss of MYC's ability in transcriptional regulation. By integrating large-scale post-perturbation transcriptomic profiling from the CMAP database, we screened over 8300 drug-induced profiles and identified 70 recurrent compounds that are predicted to antagonize MYC's transcriptional

SUBMITTER: Aceto A 

PROVIDER: S-EPMC12639535 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature