Descrizione del progetto
La profilazione delle proteasi extracellulari supporta la diagnostica basata sulle proteasi e le terapie tumorali mirate
Le proteasi sono enzimi, essi stessi proteine, che scindono o demoliscono altre proteine. Hanno funzioni essenziali nell’organismo sano e alcune proteasi extracellulari svolgono un ruolo fondamentale anche nella progressione dei tumori. Il monitoraggio dell’attività delle proteasi in vivo sarebbe di supporto alla diagnostica, alla prognostica e alla terapia, ma è molto difficile da effettuare con un elevato grado di sensibilità e selettività. Il progetto PROTECT, finanziato dall’UE, affronterà questa sfida con una piattaforma unica e completa per la diagnostica e la terapia personalizzata del cancro. La piattaforma consentirà di monitorare l’attività delle proteasi, di elaborare profili di proteasi specifici per il tumore e di somministrare farmaci in modo mirato.
Obiettivo
Proteases are involved in all hallmarks of cancer and are key regulators of tumor progression. The difficulties to monitor protease activity in vivo with sufficient sensitivity and selectivity make development of protease targeting cancer drugs and implementation of protease activity as a diagnostic and prognostic biomarker very challenging. The aim of PROTECT is to develop a novel comprehensive protease activity profiling platform for cancer-associated extracellular proteases that can address the main limitations of current strategies for in vivo protease activity monitoring with the ambition to enable a dramatic increase in sensitivity and multiplexing capabilities. We will design Liposomal Activity-Based Sensors (LABS) that can amplify proteolytic cleavage by triggering release of liposome encapsulated synthetic biomarkers. We will further leverage the possibilities to extract tumor specific protease profiles for development of personalized protease-triggered liposomal drug delivery vehicles (PROVES) for precision medicine. Sophisticated protease-responsive membrane active peptides (proMAPs) will be developed to couple protease activity to biomarker and drug release. Methods to correlate biomarker release patterns to protease activity profiles in 3D breast cancer models will be explored. The PROTECT platform can then rapidly be repurposed for precision drug delivery. The PROVES concept will combine the excellent properties of liposomes for drug delivery and the optimal combination of proMAPs, based on the protease activity profile retrieved from the LABS, for optimized protease-triggered liposomal drug release. Combined, the LABS and PROVES concepts represent a unique and comprehensive platform for diagnostics and personalized cancer therapy. The proposed work goes far beyond stat-of-the-art and will address a significant and real bottleneck that hampers drug development and exploitation of proteases as diagnostics and prognostic cancer biomarkers.
Campo scientifico
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-AG - HORIZON Action Grant Budget-BasedIstituzione ospitante
581 83 Linkoping
Svezia