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.
Project coordination
Toufic RENNO (Centre de Recherche en Cancérologie de Lyon)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
BBS Biologie et biotechnologies pour la santé
CRCL Centre de Recherche en Cancérologie de Lyon
Vidium Solutions
IGFL INSTITUT DE GENOMIQUE FONCTIONNELLE DE LYON
Help of the ANR 568,714 euros
Beginning and duration of the scientific project:
September 2022
- 36 Months