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
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-AG-UN - HORIZON Unit GrantCoordinator
10124 Torino
Italy