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Next-Generation Drug Discovery Platform for Targeting Cancer Stem Cell Pathways

Objective

Colorectal cancer (CRC) is one of the most frequent cancers with a high burden on society. In Europe alone, more than 340,000 people are diagnosed with colorectal cancer each year. While treatment options of CRC have expanded over the last decades, the survival rates of patients suffering from advanced-stage cancers remain poor. Stemness of neoplastic cells has been proposed as a major factor in treatment resistance and high relapse rates, however, drugs targeting stem cell signaling pathways in cancer are still lacking today. We propose developing and validating a new drug discovery platform based on patient-derived organoids (PDOs) and machine learning-assisted phenotypic target validation and drug discovery. Using this platform, we have previously shown that we can identify a broad spectrum of phenotypes beyond lethality, including drug-induced changes in stemness of PDOs. As part of the EIC Open Transition project, we will validate our next-generation platform for identifying therapeutics to target stem cell signaling pathways in CRC. Based on results by us showing that an interaction of MEK and Wnt signaling shifts the balance between stemness and differentiated cells, we will target Wnt pathways as a demonstrator for the technology. The ACHILLEUS project targets critical vulnerabilities in cancer and is based on technologies and approaches developed during previous ERC Advanced and ERC Proof-of-Concept grant-funded projects. The project?s ultimate aim is to spin out a NewCo as a phenotypic drug discovery platform for targeting cancer stem cell pathways.

Coordinator

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Net EU contribution
€ 2 433 125,00
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Non-EU contribution
€ 0,00