Descrizione del progetto
Biomarcatori innovativi per la diagnosi del cancro ovarico
La maggior parte delle pazienti affette da cancro ovarico manifestano metastasi al momento della diagnosi, il che richiede l’individuazione di biomarcatori innovativi per effettuare una diagnosi tempestiva. Il progetto KLKs4OvCa, finanziato dall’UE, si concentrerà sulle peptidasi correlate alla callicreina, una famiglia di enzimi coinvolti in un ampio spettro di processi biologici. Poiché le peptidasi correlate alla callicreina risultano sovraregolate nel cancro ovarico e associate a prognosi infauste, gli scienziati si propongono di svelarne il ruolo nella malattia investigandone l’attività. I risultati del progetto stabiliranno il valore prognostico e terapeutico di tali biomarcatori, contribuendo ad affrontare la sfida della diagnosi tempestiva del cancro ovarico.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
SW7 2AZ LONDON
Regno Unito