Targeting the Oncogenic Function of Myc in vivo

Información del proyecto

TarMyc

Identificador del acuerdo de subvención: 759139

DOI

10.3030/759139

Proyecto cerrado

Fecha de la firma de la CE 15 Septiembre 2017

Fecha de inicio 1 Marzo 2018

Fecha de finalización 31 Agosto 2023

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 497 905,00

Aportación de la UE

€ 1 497 905,00

Coordinado por

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Germany

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

Período documentado: 2022-09-01 hasta 2023-08-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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.