Prostate cancer under the microscope

This article was produced for the "Eureka" section of Omalius magazine #32, March 2024.

Prostate cancer is the most common cancer in Western men. In the European Union, no fewer than 335,000 new cases are detected each year, and nearly 70,000 deaths are attributed to it.

Yet, despite major advances in its detection and management, this cancer remains poorly understood. The cause is multifactorial origins and great heterogeneity between patients. The ambition of the MSCA doctoral training network is therefore to improve this understanding, while training the next generation of researchers, thanks to a pooling of multidisciplinary expertise.

During 4 years, the PROSTAMET program will bring together 15 partners made up of European universities and biomedical companies, to develop new molecules active against cancer. "This type of research is complex, particularly when it comes to designing new drugs", clarifies Catherine Michaux, FNRS senior research fellow and professor at UNamur. "Different skills are needed: biologists, chemists, pharmacists... It's this multidisciplinarity that makes this project so interesting."

With this in mind, PROSTAMET will focus on the central role of lipids. "Within cancer cells, many biochemical pathways are disrupted, including lipid metabolism", summarizes Catherine Michaux. "And the research team at KU Leuven, specialized in lipid metabolism and coordinator of the project, has already identified several enzymes that could become new targets in the treatment of prostate cancer."

Three working groups will work in parallel. The first will focus on studying the changes taking place in lipid metabolism within prostate cancer, while the second will explore in vivo key points in this metabolism and potential cancer biomarkers. "My working group, meanwhile, will focus on an enzyme involved in lipid metabolism", develops Catherine Michaux. This enzyme, aldehyde dehydrogenase 1A3, is involved in the resistance of cancer cells to ferroptosis, a type of cell death."And as a biochemist, I'll be studying its structure in space with the aim of imagining what type of molecule might come along to block its mode of operation", she continues.

In particular, the researcher will be working in collaboration with the Italian company IRBM, as well as a laboratory at the Universitad del Piemonte Oriental, in Italy. "Our skills are complementary, and my laboratory stands out, among other things, for our know-how in molecular modeling ", she points out.

This will enable the researcher to computer simulate protein blockade using small molecules, before verifying these results experimentally. "Modeling saves precious time and resources", she judges. "It avoids unnecessary testing of quantities of products, but also, by choosing only molecules that have already been selected for other medical uses, arrives more quickly at a potential drug."

In addition to the search for new treatments, the PROSTAMET program is also, and above all, a cutting-edge training program for new PhD students. "Nine PhD students will be selected for this program, and all of them will have to be on mobility", says Catherine Michaux. "This means that the one who will work in my laboratory will come from abroad, but also that all of them will be required, during their thesis, to spend a few months in another partner laboratory."

In addition, the students will visit several hospitals and laboratories, and will be required to attend several summer doctoral schools focused on the study of cancer. On the program are courses on ethics, data analysis and AI in drug design assistance. "This is an intensive program, which will give these future researchers invaluable skills for their careers," believes Catherine Michaux.

Omalius: How is cancer research organized at UNamur?

Carine Michiels: All this research is grouped within the NARILIS Institute. It is shared by both researchers and members of the CHU UCL Namur de Mont-Godinne. This enables rich interactions between basic research and clinicians, and the development of translational research.

O. : What aspects does UNamur cover?

C.M. : There are mainly five. The first concerns the study of cancer cell resistance to different treatments. Then there are studies into the role of viruses in cancer induction, and others into their interaction with senescent cells. And finally, there's work on metabolomics.

O. : You mentioned five areas...

C.M. : The last is undoubtedly the most developed. This is radiotherapy. We have a particle gas pedal, unique in the Wallonia-Brussels Federation, which enables us to carry out studies into the effects of proton therapy on the different cell types that make up a tumor. In particular, they have demonstrated real added value compared with conventional X-ray radiotherapy.

For many years now, the university community and its partners have been mobilizing in support of Operation Télévie and cancer research. All donations collected are donated to the FNRS.