Dr François CHERIFI, medical oncologist at the Centre Baclesse, has been awarded a prestigious fellowship by Gilead Sciences atESMO 2025. Worth $180,000, the award will provide two years' funding for innovative work on triple-negative breast cancer, a particularly aggressive form of breast cancer.
Background: triple-negative breast cancer, a major challenge
Breast cancer is the most common cancer in women, with almost 2.3 million new cases worldwide each year, and 670,000 deaths. Among its forms, triple-negative breast cancer stands out for its severity:
- It represents the most aggressive subtype of breast cancer.
- The risk of recurrence is higher than for other forms, and mortality remains high.
- Younger women develop it more often.
It is most often linked to familial forms with BRCA gene mutations.
New treatments: PARP inhibitors and their challenges
PARP inhibitors represent a promising therapeutic advance for this type of cancer. They are prescribed in both metastatic and adjuvant settings for patients with a germline BRCA mutation.
A germline mutation is a DNA change that affects all the patient's cells (unlike tumor mutations, which occur only in cancer cells). Patients with a germline BRCA mutation have fragile DNA repair mechanisms (notably homologous recombination), making PARP inhibitors highly effective.
However, the latest research in the field shows efficacy even in the absence of a germline BRCA mutation, raising the crucial question of the right targeting of patients: it is becoming necessary to identify precisely who could benefit from these innovative, well-tolerated treatments.
The award-winning project: towards a companion test to personalize treatments
Dr. François CHERIFI's project, entitled "Evaluation of homologous recombination deficiency and response to PARP inhibitors in triple-negative breast cancer using patient-derived tumor organoids and a companion diagnostic test", aims to address this need.
Its aim: to create and validate a companion test capable of guiding the choice of treatment for each patient.
This work is based on several complementary axes:
- Analyze the efficacy of PARP inhibitors using innovative models, including patient-derived organoids, to identify new markers for predicting response to treatment.
- Test and compare several methods for assessing HR (homologous recombination) status: DNA sequencing, GIScar score, RECAP functional test on tumor organoids, and relate these results to sensitivity to PARP inhibitors during direct exposure of organoids to treatments.
- Develop and optimize study models: in the first phase, organoids derived from xenografts* of triple-negative breast cancer patients will be used to "run-in" and compare different methods of assessing HR status. In a second phase, the analyses will be replicated on organoids derived directly from patients, supplied via the Centre Baclesse's TRIPLEX study, in order to confirm and refine the results obtained.
- In-depth exploration of biological mechanisms: a detailed analysis of markers and mechanisms associated with sensitivity (but also resistance) to PARP inhibitors will be carried out (see study diagram below).
A collaboration of excellence and international recognition
This project is made possible by a unique collaboration between the Centre Baclesse, the ORGAPRED platform (ANTICIPE), Cancer and Brain Genomic (INSERM 1245) and theInstitut Curie. It is led by Dr François CHERIFI, under the supervision of Dr Georges ÉMILE and Louis-Bastien WEISWALD, recognized experts in oncology and tumor biology.
This $180,000 grant, awarded as part of GILEAD's Research Scholar Programme, testifies to the quality and impact of the study conducted in Caen, for the benefit of patients with triple-negative breast cancer. A further step towards personalized medicine and the hope of significantly improving the care and prognosis of the women concerned.
Xenotransplantation is the use of a graft, i.e. an organ, tissue or cell, taken from an animal for transplantation into a human or between two different living species. This technique is used in the study to test treatments on a larger number of organoids.
