Project description
Overcoming chemoresistance in breast cancer
Natural killer (NK) cells are key effectors of the innate immune system, capable of destroying cancer cells without prior sensitisation. However, tumours that become resistant to chemotherapy often evade NK cell surveillance. Understanding and reversing this immune evasion is critical for improving outcomes in aggressive cancers like triple-negative breast cancer (TNBC). With the support of the Marie Skłodowska-Curie Actions programme, the NatK project aims to investigate how NK cell function is altered in chemoresistant TNBC. To identify immune-related signatures of resistance, researchers will use spatial transcriptomics and patient-derived organoids. They also plan to enhance NK cytotoxicity through gene-targeted interventions and combine it with chemotherapy to target chemoresistant TNBC.
Objective
Chemotherapy resistance remains a major challenge in cancer treatment, often leading to poor patient outcomes. NatK aims to (1) identify predictive signature of chemoresistance and (2) develop innovative therapeutic strategies to overcome it, using triple negative breast cancer (TNBC) as a model. The focus is on natural killer (NK) cells, hypothesising that reactivating these cells could enhance their cytotoxicity against chemoresistant tumours.
State-of-the-art 10X Visium spatial transcriptomics will be employed to analyse primary TNBC samples from chemotherapy responders and non-responders, mapping NK cell infiltration and activity within the tumour microenvironment (TME). Advanced bioinformatics will identify immune-related signatures of chemoresistance, validated in independent patient cohorts to develop a robust NK cell-related biomarker for patient stratification.
To translate these findings into therapeutic strategies, specific genes upregulated in chemoresistant tumours will be targeted to enhance NK cell-mediated cytotoxicity. Co-culture systems with NK cells and patient-derived organoids will be used to evaluate the impact of gene modulation, followed by the development of small molecule inhibitors targeting promising candidates. The efficacy of combining NK cell activation with chemotherapy will then be assessed both in vitro and in vivo, aiming to establish a novel combination therapy to combat chemoresistance.
NatK integrates state-of-the-art spatial transcriptomics, functional immune profiling and patient-derived organoid models to elucidate chemoresistance mechanisms. The insights gained may have broader implications, potentially extending to other cancer types and guiding targeted immunotherapy development. In line with the MSCA Postdoctoral Fellowship objectives, this interdisciplinary research will advance expertise in cutting-edge biomedical technologies, foster international collaboration, and contribute to advancing oncology in Europe.
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.
You need to log in or register to use this function
Keywords
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
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.
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
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.
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
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
BS8 1QU BRISTOL
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.