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

Project description

Novel drug-discovery platform to target cancer stem cells

Hundreds of thousands of people are diagnosed each year with colorectal cancer (CRC). Despite available treatments, the survival of patients with advanced-stage CRC is poor. The EU-funded ACHILLEUS project aims to develop and validate a novel drug discovery platform that involves patient-derived organoids (PDOs) and phenotypic machine learning-assisted validation to identify therapeutics to target CRC stem cell signalling pathways. Researchers will target CRC stem cell signalling pathways to shift the balance between stem cells and differentiated cells, using the targeting of the Wnt pathway as a proof of principle. The goal is to create a new company based on a phenotypic drug discovery platform for targeting cancer stem cell signalling.


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.


Net EU contribution
€ 2 433 125,00
Im neuenheimer feld 280
69120 Heidelberg

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Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Other funding
€ 0,00