Project description
Advanced preclinical tumour organoid models of colorectal cancer
The development of efficient therapies for patients with metastatic colorectal cancer (CRC) suffers from the lack of preclinical models. Previously, the project team developed a genetic mouse model of advanced CRC in immunocompetent mice, resulting in a biobank of mouse tumour organoids (MTOs) derived from mice bearing genetic alterations in four genes associated with CRC progression: WNT, EGFR, p53 and TGF-beta. The EU-funded CRC-MTOs project is creating a more complete MTO biobank that recreates the existing preclinical models of advanced CRC and extends the model collection using genome editing tools. These newly generated MTOs will represent unique tools to aid in the development of new drugs for advanced CRC treatment.
Objective
Colorectal cancer (CRC) is one of the leading causes of death by cancer, which is largely associated to metastatic spread of the disease. Progress to develop efficient therapies, including immunotherapies, for patients with metastatic CRC has been hampered by the lack of preclinical models to study late stage CRC in an immunocompetent background. We have developed the first genetic mouse model of advanced CRC in immunocompetent mice. This model is based in a biobank of mouse tumor organoids (MTOs) derived from tumors arising in compound mice bearing genetic alterations in 4 driver genes associated to CRC progression: WNT, EGFR, p53, and TGF-beta signaling. We have demonstrated that these MTOs represent an invaluable tool for basic and pre-clinical research in CRC, in particular to test immunotherapies (Tauriello et al., Nature 2018).
Despite its potential, the MTO biobank has limitations for translational research. They were generated as academic tools which has prevented their use in technology transfer projects and collaborations with pharmaceutical companies. In addition, they do not cover all the different CRC subtypes. We propose to create an improved and more complete second-generation MTO biobank that a) recreates the described pre-clinical model of advanced CRC, b) extends the model collection to other subsets of CRCs by means of genome editing tools and c) grants freedom to operate. These newly generated MTOs will represent unique tools ready to be licenced and exploited in strategic public-private collaborations with the final goal to aid in the development of new drugs to treat advanced CRC patients.
Fields of science
Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
08028 Barcelona
Spain