Targeting the Oncogenic Function of Myc in vivo

Projektinformationen

TarMyc

ID Finanzhilfevereinbarung: 759139

DOI

10.3030/759139

Projekt abgeschlossen

EK-Unterschriftsdatum 15 September 2017

Startdatum 1 März 2018

Enddatum 31 August 2023

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 497 905,00

EU-Beitrag

€ 1 497 905,00

Koordiniert durch

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Germany

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

Berichtszeitraum: 2022-09-01 bis 2023-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.