Novel Anti-Cancer Retro-Engineering strategy – NACRE

We have identified a novel protein-protein interaction of the ERK MAP kinase with MyD88, an adaptor of inflammatory signaling, and showed that this interaction is required for Ras-dependent cancers. We developed a small molecule, EI-52, which induces apoptosis of cancer cells and inhibits tumor growth in vivo. EI-52 also activates NF-kB, leading to an anti-tumoral immune response. However, the mechanism underlying this response is unknown. Here, we propose a dynamic, coordinated multi-omics approach measuring the kinetics of protein-protein interactions, transcription, and protein regulation following treatment with EI-52. Based on these data, we will use innovative retro-engineering inference, in silico modeling, and machine learning analysis to reconstruct the white-box mechanistic model of biochemical events leading to immunogenic cell death. This model will be used for new therapy development, diagnosis, or decision support.