Targeting the Oncogenic Function of Myc in vivo

Project Information

TarMyc

Grant agreement ID: 759139

DOI

10.3030/759139

Project closed

EC signature date 15 September 2017

Start date 1 March 2018

End date 31 August 2023

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 497 905,00

EU contribution

€ 1 497 905,00

Coordinated by

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Germany

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

Reporting period: 2022-09-01 to 2023-08-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.