Descrizione del progetto
Informazioni sulla malattia residua del cancro del colon-retto
La maggior parte dei pazienti con cancro del colon-retto (CRC, Colorectal Cancer) viene sottoposta a resezione chirurgica come prima linea di trattamento. Tuttavia, quasi il 40 % dei casi recidiva con malattia metastatica e ha una prognosi sfavorevole. Gli scienziati del progetto residualCRC, finanziato dall’UE, mirano a sviluppare nuove strategie riguardanti la malattia residua studiando le cellule tumorali che si sono diffuse in altri organi. A tal fine, impiegheranno topi e organoidi mutanti che riproducono le caratteristiche principali del CRC metastatico umano. Eseguiranno inoltre il profilo trascrizionale a livello di singola cellula e analizzeranno l’influenza delle mutazioni driver e delle risposte immunitarie sul comportamento delle cellule tumorali disseminate.
Obiettivo
Disease relapse is a major complication in colorectal cancer (CRC). At the time of diagnosis, the majority of patients will present with locoregional disease that can be effectively resected by surgery. This intervention is sufficient to cure the primary disease in most cases. Yet, over the course of the following months or years, around 40% of the patients that underwent resection of the primary tumor with curative intention will relapse, generally in the form of metastatic disease. As these metastases eventually interfere with the function of vital organs such as the liver and lungs, patients that undergo relapse have poor prognosis. Recurrent cancer arises from clinically occult tumor cells that have disseminated to foreign organs (disseminated tumor cells or DTCs) before surgical removal of the primary CRC. Although the time window between surgery and relapse offers a good opportunity to prevent metastasis, current therapies are not effective at eliminating DTCs. Thus, there is an important unmet need to develop strategies to target residual disease. Advances in this area will benefit a large proportion of patients.
Despite its clinical relevance, the study of residual disease in CRC has been largely neglected and the principles that govern the behavior of DTCs remain unknown. The main reason for this important knowledge gap is that residual tumor cells are difficult to study in patients, as they remain clinically occult. We have recently generated a unique set of compound mutant mice and organoids that reproduce key features of human metastatic CRC. We propose to leverage these new models to study the biology of residual disease. We will characterize the features of DTCs using single cell transcriptional profiling, analyze the influence of driver mutations on DTC behavior, explore mechanisms of immune evasion during the latency phase, and model DTC latency in vivo and in vitro. Our ultimate goal is to design therapies that prevent disease relapse in CRC.
Campo scientifico
Parole chiave
Programma(i)
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Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
08028 Barcelona
Spagna