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Unraveling redox regulation in cancer stem cells as a potential therapeutic target for breast cancer

Projektbeschreibung

Auf den Stoffwechsel von Krebsstammzellen abzielen

Krebsstammzellen besitzen ähnliche Merkmale und Eigenschaften wie normale Stammzellen, wie etwa die Selbsterneuerung und die Fähigkeit, fast alle Zellen in einem Tumor hervorzubringen. Angesichts der Rolle von Krebsstammzellen bei der Tumorinitiierung und bei Rückfällen konzentrierten sich die Forschungsbemühungen auf die Beschreibung der Schlüsselmechanismen in diesen Zellen. Über das im Rahmen der Marie-Skłodowska-Curie-Maßnahmen finanzierte Projekt STEMOX soll speziell die Rolle des Stoffwechsels in Krebsstammzellen untersucht werden. Hierfür werden die Forschenden von Erkrankten stammende Organoide verwenden, um die Regulation von Redox-Stoffwechselreaktionen und die Produktion von reaktiven Sauerstoffspezies genauer zu betrachten. Diese Ausrichtung könnte einen neuen Weg bereiten, um Krebsstammzellen bei Brustkrebs zu eliminieren und die Wahrscheinlichkeit eines Rückfalls zu minimieren.

Ziel

ABSTRACT Breast cancer (BC) is the most frequently diagnosed cancer and the first cause of cancer death in women worldwide. In many tumors, including BC, there is a population of cancer stem cells (CSCs) characterized for unlimited self-renewal and being resistant to conventional cancer therapies eventually leading to tumor relapses and metastases. Breast CSCs (BCSCs) show high cellular plasticity and are capable of shifting between a proliferative epithelial-like (E) state and a quiescent mesenchymal-like (M) state. This plasticity of BCSCs facilitates their ability to initiate and grow primary tumors, invade the basement membrane, traverse tissue vasculature, and ultimately colonize distant organs to form clinically significant metastases. It has been recently proposed that redox regulation might play a significant role in BCSCs plasticity and aggressiveness. We hypothesize that the redox-regulated BCSC plasticity and the highly oxidative metabolism of E-BCSCs might be a vulnerability that could be exploited as a novel BC therapy. We aim to characterize BCSCs in terms of individual ROS production, transducing our breast cancer patient-derived organoids (PDOs) collection with genetically-encoded redox sensors. We will treat breast cancer PDOs with conventional chemotherapy and inhibitors of PI3K to study changes in redox signaling occurring in the tumor. Finally, we will attempt to target these cells and modulate their redox regulation in order to differentiate and eliminate them. We expect to better understand the redox-regulation of BCSCs, to subsequently modulate BCSC redox state to target and eliminate these cells, increasing conventional therapy effectiveness and decreasing the minimal residual disease and cancer spread in BC patients, contributing to overall survival.

Koordinator

UNIVERSITA DEGLI STUDI DI TORINO
Netto-EU-Beitrag
€ 172 750,08
Adresse
VIA GIUSEPPE VERDI 8
10124 Torino
Italien

Auf der Karte ansehen

Region
Nord-Ovest Piemonte Torino
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
Keine Daten

Partner (1)