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CORDIS

Colorectal Cancer Mouse Tumor Organoids as Pre-clinical Models for Therapeutical Testing

Descrizione del progetto

Avanzati modelli tumorali preclinici con organoidi per il cancro del colon-retto

Lo sviluppo di terapie efficienti per pazienti affetti da cancro del colon-retto (CRC, colorectal cancer) metastatico è ostacolato dalla mancanza di modelli preclinici. In precedenza, il team del progetto ha sviluppato un modello murino genetico di CRC in fase avanzata in topi immunocompetenti, che ha portato a una biobanca di organoidi tumorali murini (MTO, mouse tumour organoid) derivati da topi caratterizzati da alterazioni genetiche in quattro geni associati alla progressione del CRC: WNT, EGFR, p53 e TGF-beta. Il progetto CRC-MTOs, finanziato dall’UE, sta creando una biobanca di MTO più completa che ricrea i modelli preclinici esistenti del CRC in fase avanzata e amplia la raccolta di modelli mediante l’impiego di strumenti per l’editing genomico. Questi nuovi MTO rappresenteranno strumenti unici per facilitare lo sviluppo di nuovi farmaci per il trattamento del CRC in fase avanzata.

Obiettivo

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.

Meccanismo di finanziamento

ERC-POC - Proof of Concept Grant

Istituzione ospitante

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Contribution nette de l'UE
€ 149 955,00
Indirizzo
CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
08028 Barcelona
Spagna

Mostra sulla mappa

Regione
Este Cataluña Barcelona
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 149 955,00

Beneficiari (1)