Projektbeschreibung
Ein neues molekulares Ziel für Krebs
Heparansulfat ist ein Kohlenhydrat mit einer vielseitigen Struktur, das an Proteinen auf der Zelloberfläche und in der extrazellulären Matrix andockt. Neue Hinweise deuten darauf hin, dass dieser Mechanismus bei Krebs aus dem Gleichgewicht kommt und sich auf die Wechselwirkungen zwischen den Krebszellen und der Tumormikroumgebung sowie zwischen den Krebszellen und dem Immunsystem auswirkt. Das fördert das Voranschreiten des Krebs und der Metastasierung. Das im Rahmen der Marie-Skłodowska-Curie-Maßnahmen finanzierte Projekt HEPINIB schlägt vor, das Enzym Heparanase als Wirkstoffziel zu setzen. Dieses Enzym spaltet Heparansulfat und trägt zur Remodellierung der extrazellulären Matrix bei. Die Arbeitshypothese besagt, dass Heparanase als Behandlungsziel auf vielen Ebenen funktionieren wird und die Metastase, Angiogenese und Entzündungen hemmt.
Ziel
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.
Wissenschaftliches Gebiet
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-TMA-MSCA-SE - HORIZON TMA MSCA Staff ExchangesKoordinator
48149 MUENSTER
Deutschland