Project description
Predicting drug resistance in breast cancer
The most common type of breast cancer expresses hormone receptors for oestrogen and/or progesterone (HR+) but not the HER2 protein (HER2-). This means that cancer cell growth is hormone-driven and may respond to endocrine therapies coupled with cell cycle inhibitors. However, drug resistance remains a major obstacle, limiting long-term efficacy. With the support of the Marie Skłodowska-Curie Actions programme, the CARABELA-NF1 project builds on insights from previous discoveries linking Neurofibromatosis type 1 (NF1) gene loss to drug resistance. Researchers will sequence circulating tumour DNA to detect genetic alterations linked to therapy response and resistance. The project will validate whether the NF1 gene loss may serve as a predictive signature for drug resistance in HR+/HER2- breast cancer.
Objective
HR+/HER2- breast cancer (BC) patients often show limited response to current neoadjuvant chemotherapy, highlighting the critical need for alternative therapeutics strategies. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard of care in adjuvant treatment for HR+/HER2- BC, with the potential for significantly improved outcomes in the neoadjuvant setting. However, drug resistance remains a significant challenge, with a critical need for early-stage biomarkers to predict resistance. The CARABELA phase 2 clinical trial, led by Dr. Emilio Alba (the supervisor of this proposal), provides valuable data on the efficacy and resistance patterns of prolonged CDK4/6i plus ET in neoadjuvant settings. Previous research by Dr. Chica-Parrado (the candidate) identified NF1 loss-of-function (LOF) mutations as key drivers of resistance to both ET and CDK4/6i. The CARABELA-NF1 study aims to leverage this expertise to integrate preclinical data with clinical insights from the CARABELA trial. The objectives of CARABELA-NF1 project are: (1) To perform targeted sequencing of circulating tumor DNA (ctDNA) to identify genomic alterations associated with resistance to CDK4/6i or ET and correlate these with clinical responses. (2) To develop an NF1-loss signature (NF1sig) from cell line data and validate this predictive signature using RNA from pre-treatment samples in the CARABELA trial. (3) To conduct drug screening in HR+/HER2- BC organoids derived from patients resistant to ET and CDK4/6i with NF1 mutations, focusing on the activation of pathways induced by the treatment.
This project combines advanced genomic profiling with clinical trial data and drug screening to address the pressing need for effective biomarkers and novel therapeutic strategies in the neoadjuvant setting for HR+/HER2- BC.
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 mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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)
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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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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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(opens in new window) HORIZON-MSCA-2024-PF-01
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29590 MALAGA
Spain
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