Descripción del proyecto
Una herramienta mejor para el tratamiento del cáncer de páncreas
El adenocarcinoma ductal pancreático (ADP), que representa el 90 % de los casos de cáncer de páncreas, tiene una elevada tasa de mortalidad. Sin embargo, las investigaciones llevadas a cabo en los últimos treinta años se han centrado principalmente en caracterizar y comprender las propiedades de las células cancerosas del ADP, sin prestar atención a su contexto celular específico. Es importante señalar que el ADP está formado por un 80 % de células no tumorales. En el proyecto S-Target-in-PANR, financiado por el Consejo Europeo de Investigación, se demostró que la valoración de un candidato específico, PAP/REG3A, en el suero puede ser un biomarcador para estratificar el ADP y optimizar el tratamiento de los pacientes mediante la predicción de la resecabilidad. En el proyecto pBioStrat-for-PDA, financiado por el Consejo Europeo de Investigación, se validará este hallazgo utilizando cohortes sólidas y métodos de ensayo adaptados.
Objetivo
With an overall 3-year survival rate of only ~6% together with an increased incidence pancreatic ductal adenocarcinoma (PDA), which represents 90% of pancreatic cancer, figures as the solid cancer with the worst prognosis. In trying to understand “the” reason for such negative outlook, one has to consider that the fundamental and clinical research conducted during the last 30 years has focused on characterizing and understanding the properties of the PDA cancer cells, neglecting the specific cellular context of those tumors. Indeed PDA consists of 80% of non-tumor cells. In the ERC Starting grant, S-Target-in-PANR, I conducted from 2011 to 2016 we took into account this specificity and analyzed the impact of this stromal compartment on PDA physiology. The discoveries and conceptual progresses obtained throughout the S-Target-in-PANR programme opened new potent improvements of PDA patients’ management. Among them, we revealed that one of the candidates, PAP/REG3A, was secreted by acinar cells from the peri-tumoral microenvironment to enhance peri-neural invasion ability of tumor cells. Interestingly, we demonstrated that PAP/REG3A titration in serum was a potent biomarker in order to stratify PDA and could lead to patients’ management optimization and more specifically to predict resectability.
This validation, using robust cohorts and adapted testing, constitutes the main goal of our ERC-PoC pBioStrat-for-PDA. Indeed, it will provide a powerful tool for clinicians in order to better determine the resectability of a tumor by taking into account its biological nature on top of the only clinical criteria used so far. As a consequence the use of a non-invasive PAP/REG3A serum level determination will improve patients’ managements by (1) shortening the delay to start palliative chemotherapy, (2) limiting unnecessary surgery with important mortality/morbidity and (3) improving their redirection to adapted clinical trials, as the one targeting JAK2/STAT3 signalling.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
75654 Paris
Francia