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Unraveling redox regulation in cancer stem cells as a potential therapeutic targ...

Unraveling redox regulation in cancer stem cells as a potential therapeutic target for breast cancer 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 unlimite... ver más

31/03/2025

UNITO

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UNIVERSITA DEGLI STUDI DI TORINO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-01

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021 ExpectedOutcome:

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Duración del proyecto: 23 meses Fecha Inicio: 2023-04-01
Fecha Fin: 2025-03-31

Líder del proyecto

UNIVERSITA DEGLI STUDI DI TORINO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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