SCK CEN tackling the most aggressive breast cancer
EU-wide project Accelerate.EU works on new treatment option for triple-negative breast cancer
In a brand new EU-wide project, 17 partners are joining forces to develop more effective treatments for aggressive cancers. One type is triple-negative breast cancer: this form of cancer mostly affects young women and is currently difficult to treat. The nuclear research centre SCK CEN is taking the lead in preclinical research in this project. This research is intended to show whether radiopharmaceuticals – containing astatine-211 – can efficiently eliminate aggressive breast cancer. The ultimate goal is to take the treatment from preclinical research to clinical trials and eventually to patients.
Triple-negative breast cancer is an aggressive form of breast cancer that often affects young people, growing and also spreading rapidly. In most breast cancers, oncologists find the female sex hormones – oestrogen and progesterone – and the protein HER2, which influence tumour growth. However, this form of cancer lacks those three substances, which is why triple-negative breast cancer does not respond to hormone therapy, targeted cancer treatment with HER2 inhibitors or even traditional chemotherapy. With metastases, 5-year survival rates drop dramatically from 77% to just 12%. "Due to rapid tumour growth, treatment resistance and high mortality rates, different, more effective treatments are urgently required for this type of cancer. And with this EU-wide project, Accelerate.EU, we are making that happen. We want to offer new prospects to patients with triple-negative breast cancer," explains Kevin Tabury, expert in radiobiology at SCK CEN.
SCK CEN aims to identify Radioligand Therapy as an effective treatment option for this form of breast cancer. Before treatments are given to patients, they go through an extensive development process, which is intended to demonstrate the effectiveness and safety of radiopharmaceuticals, and it all invariably starts with preclinical research. "We are taking the lead in this preclinical research and conducting it in close collaboration with Jules Bordet Institute," he continues.
Astatine-211 as a travel companion
What exactly does Radioligand Therapy involve? In this process, a carrier molecule transports a radioisotope to the tumour and at the same time to metastases, to enable a very localised treatment. Irina Primac, expert in radiobiology at the nuclear research centre SCK CEN explains: "In our preclinical research, we attach the therapeutic alpha emitter astatine-211 to travel along with the molecule. Astatine-211 offers the great advantage of emitting only one alpha particle when the radioisotope decays. This alpha particle has higher energy and travels only one-twentieth of a millimetre in tissue, which means we can concentrate the radiation dose even more precisely in a specific target area. That's the theory, we'll test that against reality."
SCK CEN and Jules Bordet Institute will evaluate the effect of this alpha emitter. To do this, they will examine numerous parameters, such as treatment efficacy, dose response, side effects and efficacy in combination with other therapies. "We want to understand how astatine-211 behaves in the body. How is it absorbed, distributed and re-excreted? How does it inhibit tumour growth? What is the optimal dosage to achieve the desired therapeutic effects and minimise possible side effects? Our goal is to successfully lead this therapy from preclinical research to clinical trials. And that requires, first of all, answers to those questions," she concludes. Both research partners aim to obtain those answers within two to three years, at which time Jules Bordet Institute and Institut de Cancérologie de l'Ouest plan to launch clinical trials. The clinical trials will continue at Jules Bordet Institute in Brussels, Belgium.
FAPI as a guide
The carrier molecule that guides astatine-211 to the cancer cell is known as a "FAPI" or FAP inhibitor. "To understand what FAPI is, we must first zoom in on human biology," says Irina Primac. "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," she concludes.
Accelerate.EU accelerates advent of astatine-211 in cancer treatment
The European project Accelerate.EU brings together no less than 17 European partners from the industrial, medical and scientific sectors. The consortium is not only working on a new treatment option for triple-negative breast cancer. The partners also hope to force a breakthrough in the use of astatine-211 to fight pancreatic cancer and glioblastoma. Like triple-negative breast cancer, both of these are considered very aggressive cancers. The purpose of Accelerate.EU is twofold: on the one hand, the consortium aims to take (pre)clinical research to the next stage of development — and thus one step closer to patients. On the other hand, the consortium partners want to establish reliable and decentralised production; in other words, production will take place close to the hospitals.
This is because astatine-211 has a half-life of 7.2 hours. For the patient, this translates into the major benefit that less than 1% of radioactivity remains in the body after two days. The nuclear research centre SCK CEN is only involved in the first objective of the ambitious project, as part of which it will lead the preclinical research on this aggressive form of breast cancer. The overall project is being entirely led by Belgium, with IBA and Jules Bordet Institute at the helm. Accelerate.EU has a budget of 16 million euros, half of which is funded by the European Commission.
SCK CEN is realising its ambition
By leading the preclinical research, SCK CEN is gradually 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 3 October 2024. Would you like to read the official press release?
