SCK CEN leads preclinical research on ovarian cancer
New European project seeks more effective treatment for one of the most deadly cancers in women
Ovarian cancer is not detected in 3 out of 4 women until metastases have already appeared. Treatment is difficult in advanced stages and scientists are seeking new treatment options. One potential option is Radioligand Therapy. The nuclear research centre SCK CEN is leading the way in preclinical research into this innovative therapy, in which a specially designed molecule delivers a radioisotope directly to a tumour as well as metastases. The radioisotope fights cancer cells by irradiating them. "Lutetium-177 is already achieving great results in metastatic prostate cancer and neuroendocrine tumours. Now we are studying whether terbium-161 can have a similar effect in ovarian cancer," says Koen Hasaers, director of Nuclear Medical Applications at the nuclear research centre SCK CEN. This research forms part of a brand new EU-wide project: Thera4Care.
In 2022, 70,000 women in Europe were diagnosed with ovarian cancer. Ovarian cancer has been dubbed 'the silent killer'. It is often not discovered until the tumour is already in its third or fourth stage. Over 70% of women already have metastases in the rest of the body. Five years after diagnosis, only 38% of them are still alive. Current treatments fall short of effectively treating ovarian cancer and researchers want to change that. To do this, scientists are also looking in the direction of Radioligand Therapy. This emerging, innovative cancer treatment uses radiopharmaceuticals to locally target cancer cells in the tumour while at the same time fighting metastases.
Today, radiopharmaceuticals using lutetium-177 are already achieving positive results to treat (metastatic) prostate cancer and neuroendocrine tumours. "Experience tells us that radiopharmaceuticals significantly increase the probability of therapy response, even when the disease has already spread. This offers new prospects for hard-to-treat cancers, including ovarian cancer," explains Koen Hasaers, director of Nuclear Medical Applications at the nuclear research centre SCK CEN. The research offers more than just prospects. As part of a brand new EU-wide project, Thera4Care, SCK CEN will examine the potential of radiopharmaceuticals for ovarian cancer under the microscope. "We will be leading preclinical research and we aim to have all the much-needed results on the table so that Phase 1 clinical trials can start," says Koen Hasaers. This preclinical research will be conducted in collaboration with the Paul Scherrer Institute (PSI), Policlinico Universitario Gemelli, Universitätsmedizin Klinikum Essen and the Jules Bordet Institute in Belgium.
Preclinical research
Exactly what will the nuclear research centre SCK CEN and its partners study? "To explain that, we need to zoom in on human biology for a moment," begins Irina Primac, radiobiologist at SCK CEN. "Tumours are complex tissues. When we think of cancer, we usually think of malignant cells, but they also consist of vascular cells, immune cells and fibroblasts. These fibroblasts influence numerous processes, such as tumour growth, therapy response and metastasis. However, they cannot disguise themselves or hide in the body: they are clearly distinguishable from fibroblasts in healthy tissue because they express specific proteins."
One of these is fibroblast activation protein or FAP. The transmembrane contains 760 amino acids, the largest part of which is found on the outside of the cell. These amino acids provide the ideal sites for molecules to bind onto. "FAPI, or FAP inhibitor, is a suitable molecule for targeting these cells. By binding a therapeutic radioisotope to this molecule, we can irradiate the cancer cell, thereby disrupting the DNA. The cancer cells die, and consequently the tumour will eventually shrink or disappear," Irina continues. "In our preclinical research, we evaluate the efficacy of radiopharmaceuticals. We want to find out, does the radioisotope accumulate only in the cancer environment? How does the tumour respond after radiation? At what dose is the therapeutic effect optimal?"
Higher therapeutic effect with terbium-161
However, the consortium will not pair FAPI not with lutetium-177, but instead with its oft-named successor: terbium-161. Targeted cancer therapies with terbium-161 are expected to have a higher therapeutic effect. This is because of its special properties: specifically, when the terbium-161 radioisotope decays, it immediately emits an average of two low-energy Auger electrons per beta particle. Once emitted, these electrons, like alpha particles, do not travel far. This means a higher dose can accumulate – very locally near the cancer cell – with each injection. In theory, a higher local dose translates into a higher therapeutic effect, sparing healthy tissue in the process. Preclinical research is needed to provide the evidence for this.
European project 'Thera4Care'
This preclinical research is being conducted as part of the Thera4Care project. The project involves as many as 29 European industrial parties, research centres and hospitals pooling resources to make new, innovative radiopharmaceuticals available and to use them in patient care. As part of this, the consortium is focusing on cancer types for which medical needs remain unmet. In addition, the project concentrates on several relevant radioisotopes, including terbium-161, copper-61/64, and astatine-211. The nuclear research centre SCK CEN is coordinating the preclinical research and will itself conduct preclinical research on the use of terbium-161 in the treatment of ovarian cancer, but the overall project is being led by GE HealthCare, Policlinico Universitario Gemelli and Universitätsmedizin Klinikum Essen. Thera4Care has a budget of 25.3 million euros, half of which is being funded by the European Commission.
SCK CEN is realising its ambition
By leading the preclinical research, SCK CEN is progressively realising the priority goals of its 'Exploring 2040' strategic plan. With the updated strategy, SCK CEN expressed its ambition to expand its role in tackling cancer. Its BR2 research reactor has long been an indispensable production hub for medical radioisotopes around the world. It will continue to perform this role, but SCK CEN intends to evolve into a key player both in the production of new radiopharmaceuticals and preclinical research.
All the details about our contribution in the fight against cancer can be found on our website.
The project was officially announced on 7 October 2024. Would you like to read the official press release?
Visit the website of Thera4care.
