Summary of the research project
Ovarian cancers are one of the leading causes of death from gynecologic malignancies. When these cancers can be detected early, their prognosis is quite favorable. However, most patients do not experience any specific symptoms thus, many cases are detected at a late stage of the disease, when the 5-year survival rate of patients is only slightly higher than 30%. After first line treatment, recurrences of ovarian cancer happen very frequently. Additionally, these recurrences become resistant to conventional chemotherapy agents, emphasizing the need to seek new therapeutic options for these cancers.
New innovative therapy approaches have been shown to be of particular interest for the treatment of other types of cancers. Accordingly, this Chair of Excellence in “Innovative Theranostic Approaches in Ovarian Cancers“, is inspired from the quest for new treatments in other malignancies to apply this knowledge to the development of novel therapies for ovarian cancers.
Our strategy is based on the development of theranostic agents, which combine diagnostic and therapeutic abilities. These new agents allow for an improved targeting of patients and can predict the therapeutic response using positron emission tomography (PET) imaging. Consequently, only patients who are most likely to respond to treatment will be selected and treated with theranostic agents coupled with a specific radioactive isotope for therapy (alpha emitter). Theranostic agents are designed to be specific and to only target tumor cells. Thus, radiation is delivered as close as possible to the tumor, affecting minimally its surrounding healthy tissues. Ionizing radiations creates damages in tumor cells’ DNA and consequently leads to their death.
To date, no specific theranostic agent exists for ovarian cancer and agents developed for other cancers have proven unsuccessful in ovarian tumors. Hence, we want to use ovarian tumor samples from patients to look for specific biomarkers uniquely expressed in these cancer types. By identifying these new biomarkers, we will be able to develop novel molecules that specifically target these markers and consequently tumor cells. Conjugation of these molecules with a radioactive isotope for PET imaging will allow us to define the population that will most likely respond to treatment using therapeutic isotopes.
Another part of the project of this Chair of Excellence proposal will investigate other innovative radiotherapy paradigms such as combinations of therapeutic agents with different radiation modalities in ovarian cancers. Radiation therapy alone in ovarian tumors has not shown significant benefit to patients, but when combined with chemotherapy, it improved survival rates. We will then explore the effects of different innovative therapies such as inhibition of survival pathways in combination with conventional and innovative radiotherapies (such as theranostic agents) to improve treatment efficacy and minimize morbidity in patients with ovarian cancers.
This research project has also many collaborative aspects, of course with the researchers and clinicians of the Normandie Oncologie Federative Structure, but also in an international context, since setting up of a joint laboratory with the Sherbrooke Institute of Pharmacology at the Université de Sherbrooke (Canada) is planned within the framework of this chair of excellence.