Projektbeschreibung
Neuartige Biomarker für die Diagnose von Eierstockkrebs
Bei den meisten Patientinnen mit Eierstockkrebs haben sich zur Zeit der Diagnose bereits Metastasen gebildet. Neue Biomarker für eine frühe Diagnose sind also unbedingt notwendig. Das EU-finanzierte Projekt KLKs4OvCa wird sich auf die Kallikrein-bezogenen Peptidasen (KLK) konzentrieren, eine Enzymart, die an vielen verschiedenen biologischen Prozessen beteiligt ist. KLK wird bei Eierstockkrebs überproduziert und steht mit schlechten Prognosen in Verbindung. Daher wollen die Forschenden deren Rolle bei der Krankheit ermitteln, indem sie ihre Aktivität untersuchen. Die Projektergebnisse werden den Wert dieses Biomarkers für Prognosen und Behandlungen bestimmen und dabei helfen, das Problem früher Diagnosen von Eierstockkrebs zu lösen.
Ziel
Ovarian cancer (OvCa) is one of the most fatal female gynaecological malignancies, resulting in 180,000 deaths annually. The majority of patients have metastatic disease at time of diagnosis, thus, early diagnosis of OvCa remains a challenge to our society. In addition, the low survival rates over the past decades have remained largely unchanged, evidencing the need of new therapies for OvCa. Kallikrein-related peptidases (KLKs) are a family of 14 serine proteases which form a cross activation network known as the KLK activome. KLKs show diverse tissue expression and physiological function, and aberrant KLK expression and activity has been related to several pathological conditions including skin diseases, neurodegenerative disorders and cancer. In OvCa, KLKs4,5,6 & 7 levels are upregulated and associated with its unfavourable prognosis, therefore, KLKs4,5,6 & 7 are considered potential drug targets and biomarkers for OvCa. However, KLK activity is decoupled from simple abundance, and the contribution of each KLK activity in OvCa progression remain poorly understood. In this project, I will develop selective (quenched)-Activity Based Probes ((q)-ABPs) for KLKs4,5,6 & 7 and quantify the active enzyme fraction of each KLK to determine their contribution to OvCa. Additionally, I will develop proteolysis targeting chimeras (PROTACs) which can be selectively activated by specific KLKs to unlock their potential as therapeutic targets for OvCa. This proposal aims to deliver a versatile platform to interrogate the application of KLKs4,5,6 & 7 as biomarkers and therapeutic targets for OvCa, with potential application to other KLK- and serine protease-related disorders. My participation in this proposal will allow to bring key knowledge to face the challenging objectives and receive high-quality training that will provide me with a solid and diversified groundwork to become and independent researcher in the drug discovery field.
Wissenschaftliches Gebiet
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Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
SW7 2AZ LONDON
Vereinigtes Königreich