Project description
Breast cancer 2 gene and prostate tumour response to radioligand therapy
Radioligand therapy (RLT) improved survival of patients with prostate cancer in clinical trials yet tumour response mechanisms are poorly understood. Evidence suggests that deficiencies/mutations in DNA damage response (DDR) genes could be correlated to an increased tumour cell sensitivity towards RLT. However, mutations in the breast cancer 2 (BRAC2) gene, a DDR gene, are associated with increased risk of prostate cancer, a modulation of the immune response and a poor response to RLT treatment. With the support of the Marie Skłodowska-Curie Actions programme, the BRCA-RLT project aims to investigate the impact of BRCA2 deficiency on RLT response and determine if BRCA2 status could be a biomarker responsiveness to RLT.
Objective
Despite current advances in prostate cancer (PCa) treatment, 10 to 20% of PCa will evolve to a metastatic stage, where the overall survival is 14 months. Radioligand therapy (RLT) is a new, promising treatment consisting in the injection of a radiolabelled vector. In PCa, this therapy targets Prostate Specific Membrane Antigen, which is overexpressed on PCa cells compared to other tissues. RLT has been shown to increase the overall survival of patients in clinical trials, but in order to improve its efficiency and identify possible biomarkers for patient selection, tumour response mechanisms must be studied.
Especially, some reports indicate that deficiency in DNA Damage Response (DDR) genes could be correlated to an increased sensitivity of tumour cells towards RLT. In PCa, one of the most frequent deficient DDR gene is Breast cancer 2 (BRCA2), which is correlated with bad prognosis. In addition, retrospective studies showed a potential link between BRCA2 deficiency and a modulation of the immune response, which also influences treatment response. Therefore BRCA2 deficiency could impact both the immune response and RLT outcome. In this project, I will investigate the impact of BRCA2deficiency on RLT response. Both the tumour DDR and immunogenicity will be assessed, in order to view the treatment response as a whole. These studies will be conducted in vitro in murine and human PCa cell lines and in in vivo murine model. Results of my project will show the impact of BRCA2 deficiency on RLT outcome and whether BRCA2 status could be used as a biomarker to predetermine potential good responders to RLT. Besides contributing to the fundamental scientific
advancement on the effect of BRCA2 deficiency in RLT response, I also aim to raising the awareness of these principles in the scientific community and other stakeholders such as clinicians. This will open the way to development of potential biomarker of good response to this new treatment
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.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
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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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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
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
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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-2022-PF-01
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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.
3015 GD Rotterdam
Netherlands
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