Project description
Targeting the metabolism of cancer stem cells
Cancer stem cells (CSCs) share similar characteristics and properties with normal stem cells, such as self-renewal and the ability to give rise to almost all cells in a tumour. Given the role of CSCs in tumour initiation and relapse, research efforts have focused on delineating key mechanisms in these cells. Funded by the Marie Skłodowska-Curie Actions programme, the STEMOX project aims to investigate the role of metabolism in CSCs. Using patient-derived organoids, researchers will study the regulation of redox metabolic reactions and the production of reactive oxygen species. Targeting these pathways may offer a novel way to eliminate CSCs in breast cancer and minimise the chances of relapse.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences clinical medicine oncology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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10124 Torino
Italy
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