Targeting the Oncogenic Function of Myc in vivo

Informations projet

TarMyc

N° de convention de subvention: 759139

DOI

10.3030/759139

Projet clôturé

Date de signature de la CE 15 Septembre 2017

Date de début 1 Mars 2018

Date de fin 31 Août 2023

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 497 905,00

Contribution de l’UE

€ 1 497 905,00

Coordonné par

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Germany

Periodic Reporting for period 4 - TarMyc (Targeting the Oncogenic Function of Myc in vivo)

Période du rapport: 2022-09-01 au 2023-08-31

Résumé du contexte et des objectifs généraux du projet

In ageing Western societies tumors are becoming the most relevant medical problem. Transcription factors of the Myc oncoprotein family are key players in the development of most human tumors. The central goal of TarMyc was to elucidate the critical oncogenic mechanism of MYC and to develop strategies to target MYC function for cancer therapy. By identifying critical target genes and binding partners of MYC as novel targets for cancer therapy.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

First, we developed systems to deplete MYC and MYC-associated proteins in cells and mice using both inducible shRNAs and targeted protein degradation systems. We observed that MYC regulates unique sets of genes when expressed at low, physiological, versus high, oncogenic levels. Oncogenic processes induced by MYC include angiogenesis, specific metabolic adaptations and, most importantly, immune evasion. Second, we identified and characterized MYC binding partners that are critical for the establishment of these oncogenic gene expression signatures. Third, we developed proteolysis targeting chimeras (PROTACs) for the most promising candidates and characterized their impact on tumor growth in vivo.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Overall, the TarMyc project has laid the foundation for potential new anti-MYC-based cancer therapies.

Graphical abstract in the press release about a publication of my lab in Nature Chemical Biology.