A key enzyme in the fight against resistant female cancers: Dr. Raphaël Ceccaldi’s project receives award

“This award highlights the crucial role of basic research. Understanding the mechanisms of life at the molecular level, without necessarily aiming for immediate medical application, can lead to tangible therapeutic breakthroughs. It’s a powerful recognition of science, and a real source of hope for patients.” said Dr. Raphaël Ceccaldi, head of the “Alternative DNA Repair Mechanisms in Cancers¹ ” team at Institut Curie.

In 2022, the World Health Organization estimated nearly 2.3 million new cases of breast ancer and ovarian cancer worldwide² . These aggressive cancers, which often carry a poor prognosis, remain difficult to treat due to their high genomic instability, which limits therapeutic options. In about half of all cases, these cancer cells have DNA repair defects, primarily linked to BRCA gene mutations. Unable to efficiently repair their DNA, the cells rely on alternative repair pathways to survive.

Dr. Raphaël Ceccaldi was awarded the maximum grant (€100,000) available under the EQT³ Foundation 's Breakthrough Science: Women's Health Grant program for his DISARM project, which directly targets this DNA repair deficiency. The grant supports innovative research addressing major challenges in women’s health.

This project aligns closely with the goals of the Institut des Cancers des Femmes, an initiative led by Institut Curie, PSL University, and Inserm. Its mission is to develop innovative, targeted, and personalized therapeutic approaches to cure increasing numbers of patients with female-specific cancers. 
 

New hope for treating resistant cancers

Dr Ceccaldi and his team have shown that the presence of uracil in the genome significantly compromises the survival of tumor cells in certain subtypes of breast and ovarian cancer. “Tumor cells with BRCA1/2 mutations already have impaired DNA repair capacity. Forcing uracil into the genome enables us to selectively eliminate cancer cells while preserving healthy ones,” explains the researcher.

This strategy, while especially promising for breast and ovarian cancers resistant to conventional treatments (such as PARP inhibitors or chemotherapy), may also prove effective against other cancer types with similar DNA repair abnormalities.

The grant will allow the team to develop initial drug candidates, analyze their physicochemical properties, and validate their efficacy in preclinical studies over the coming year, with the goal of identifying the most promising compounds. 

This innovative approach, already protected by several patents, is being supported by Institut Curie's Industrial Development and Partnerships Department. The goal: to unlock its full potential and make it widely accessible across multiple indications. Ultimately, the project could lead to the creation of a start-up to accelerate clinical trial development and bring this innovation to patients affected by treatment-resistant cancers.  

[1] Cancer, Heterogeneity, Instability and Plasticity unit – CHIP (Inserm U830)

[2] https://www.who.int/news-room/fact-sheets/detail/breast-cancer

[3] EQT Foundation is a philanthropic organisation and long-term shareholder of the global investment organization EQT, founded by partners at EQT. The Foundation supports scientists and entrepreneurs bringing breakthrough solutions from lab to market, combining EQT’s expertise with catalytic investments and grants. With a focus on supporting scientific progress in underfunded areas of climate and health, the Foundation provides a learning platform for EQT employees to develop and work collaboratively across the globe, while engaging in philanthropy and making a positive impact.