Descrizione del progetto
Un nuovo bersaglio molecolare per il cancro
L’eparan solfato è un carboidrato di struttura varia che si attacca alle proteine presenti sulla superficie cellulare e nella matrice extracellulare. Le prove emergenti indicano che nel cancro questo processo è deregolato e influisce sulle interazioni delle cellule tumorali con il microambiente tumorale e il sistema immunitario, promuovendo la progressione del cancro e le metastasi. Il progetto HEPINIB, finanziato dal programma di azioni Marie Skłodowska-Curie, propone di utilizzare come bersaglio farmacologico l’enzima eparanasi, che scinde l’eparan solfato e contribuisce al rimodellamento della matrice extracellulare. L’ipotesi di lavoro è che il bersaglio terapeutico dell’eparanasi agisca su più livelli, ostacolando metastasi, angiogenesi e infiammazione.
Obiettivo
Cancer is a leading cause of mortality within the aging European population. Therapeutic targeting is hampered by the complexity of the disease, which includes not only molecular changes within the tumor cell itself, but also within its microenvironment. Tumor angiogenesis, tumor-stroma interactions, interactions with immune cells, with the extracellular matrix and cancer stem cell niches
allow for malignant cell survival and promote metastasis, the leading cause for cancer-associated mortality. Proteins substituted with the heparin-related carbohydrate heparan sulfate (HS) are dysregulated in malignant diseases, and are known to modulate all of the aforementioned processes of tumor progression. Several functions of HS-PGs in tumor progression are modulated by the enzyme
heparanase (HPSE), which is barely expressed in adults, but upregulated during tumor progression, inflammation and angiogenesis, thus constituting an excellent drug target. Indeed, HPSE, the sole HS degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis and inflammation. HPSE accomplishes this by degrading HS and thereby regulating the bioavailability of heparin-binding proteins, priming the tumor microenvironment and mediating tumor-host crosstalk. We predict that therapeutic targeting of HPSE to be superior to conventional approaches, as it does not only have the potential to synchronously targeting tumor progression and metastasis at multiple levels (metastasis, angiogenesis, inflammation & immunity), but it is also be expected to have a favourable side effects profile. HEPINIB will combine leading experts of HPSE-related cancer research with non-academic partners providing a panel of innovative technologies with the aims of providing a deeper understanding of HPSE function in tumor progression, of developing novel HPSE inhibitors and delivery systems, and of trans-sectoral and interdisciplinary training of young scientists.
Campo scientifico
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-SE - HORIZON TMA MSCA Staff ExchangesCoordinatore
48149 MUENSTER
Germania