The Magician project
Ovarian cancer is diagnosed at the stage of peritoneal carcinomatosis—where metastatic spread to the peritoneum has already occurred—in 75% of cases. Even among patients who have undergone first-line treatment involving complete surgery and platinum-based chemotherapy, 75% will experience a relapse within two years. Successive relapses lead to the selection of clones resistant to platinum salts.
Mechanisms cited to explain this platinum resistance include insufficient drug penetration into metastatic nodules and efficient DNA repair activity that renders chemotherapy ineffective. Furthermore, immune checkpoint inhibitor (ICI) therapy fails to enhance the therapeutic effect due to the tumor’s low immunogenicity and limited lymphocyte infiltration.
To overcome these challenges, we propose using olaparib—a poly(ADP-ribose) polymerase (PARP) inhibitor—due to its ability to enhance tumor immunogenicity and sensitivity to immune checkpoint inhibitors (ICIs). To address issues regarding poor drug distribution and penetration within metastatic nodules, we will combine two approaches: an innovative procedure known as Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)—already in clinical use and developed in France by Prof. Pr Glehen‘s team in Lyon—and a combination of ICIs with nanoparticles loaded with platinum and olaparib, patented by LAGEPP. These experiments will be conducted using mouse models of ovarian peritoneal carcinomatosis developed on the Imthernat platform. A further objective is to adapt this technique for treating peritoneal carcinomatosis in dogs.
Project leaders:
Frédérique PONCE
Frédérique PONCE holds a veterinary degree and a PhD, and is a European specialist in oncology (ECVIM-CA (Oncology)). She is a Professor of Comparative Oncology and Director of the Oncology Division within the ICE Research Unit at the VetAgro Sup in Lyon. She currently serves as Deputy Director General of VetAgro Sup (Lyon Veterinary Campus). She established the first and only training program in France for European specialists in veterinary oncology (ECVIM-CA).
Her research has led to the development of a comparative oncology program designed to study cancer biology and novel treatments, utilizing a “One Health” approach based on translational research from animals to humans. She introduced spontaneous cancer models in companion animals to preclinical research. She established a partnership with the CLB and the CRCL and co-founded a Master’s program in oncology with the Lyon 1 Université (jointly accredited by VetAgro Sup and the Lyon 1 Université). Her oncology team is part of initiatives such as the SHAPE-Med@Lyon project and the DEVweCAN LabEx.
David KRYZA
Dr. David Kryza is a radiopharmacist (PhD) who heads the radiopharmacy unit of the LUMEN nuclear medicine department, affiliated with the Hospices Civils de Lyon and the Centre Léon Bérard. He earned his PhD in radiopharmaceutical sciences in 2007 from the University of Lyon while working at Advanced Accelerator Applications (AAA), where he developed automated synthesis methods for novel radiopharmaceuticals. In 2015, he obtained his Habilitation to Supervise Research (HDR). He is a board member of the Société Française de Médecine Nucléaire (SFMN) and a member of the SFMN’s RIV group.
His scientific work focuses on the radiolabeling and in vivo preclinical evaluation of new therapeutic molecules and nanosystems at the LAGEPP laboratory (CNRS UMR). He heads the IMTHERNAT platform—a preclinical unit equipped with advanced facilities (µSPECT-CT, µPET-CT, and optical imaging, as well as radiochemistry and animal laboratories)—dedicated to the translational development of radiopharmaceuticals from the laboratory to the clinic. He has participated in over 50 clinical trials (Phase I to III) involving diagnostic or therapeutic radiopharmaceuticals.
