Fighting tumours down to the last cancer cell

Researchers at PSI have developed a new drug that could increase the survival chances of patients with metastatic prostate cancer. The drug is now being tested on patients in the PROGNOSTICS project. A research consortium consisting of the Paul Scherrer Institute, the University Hospital Basel and ETH Zurich is receiving two million Swiss francs in funding for this project.
(Graphic: Aurel Märki)

In Switzerland, about 7100 men are diagnosed with prostate cancer every year – some 1400 of them die because the tumour has already metastasised and no longer responds to established treatments. Now there is new hope for these patients. In the PROGNOSTICS (PeRsOnalised theraGNOstics of metaStaTIC proState cancer) project, teams led by Roger Schibli of PSI, Damian Wild of the University Hospital Basel and Nicola Aceto of ETH Zurich are testing a new radioactive drug that may be more promising than existing radiopharmaceuticals. The project will receive 2 million Swiss francs in funding, of which 1.7 million will come from the ETH Domain’s strategic focus area “Personalised Health and Related Technologies”. The study is scheduled to start in July 2023, the clinical trial starts in 2024 and will run until the end of 2025.

Hope for a third of patients

About one third of patients with metastatic prostate cancer do not respond adequately to existing drugs: individual cancer cells can survive and form new metastases. In the future, new radionuclides could help such patients. The Paul Scherrer Institute has been carrying out research into a new isotope – terbium-161 – and its therapeutic uses for around 10 years now. In laboratory tests, Cristina Müller’s research group at PSI’s Centre for Radiopharmaceutical Sciences has demonstrated that the new terbium-161 can treat tumours effectively. In the context of PROGNOSTICS, this promising approach will now be tested at the University Hospital Basel on 30 patients for whom other therapies have not had the desired success.

Drugs of this type – called radiopharmaceuticals – are radioactive substances that are injected into the bloodstream. The molecules are designed to attach themselves to the surface of tumour cells, like a key in a lock, but not to healthy cells. One end of the drug carries a radioactive atom that emits electrons (beta particles) during radioactive decay. These produce aggressive radicals inside the tumour cell, i.e. highly reactive substances that can attack the cell’s genetic material and thus destroy it.

The consortium has now identified a possible reason why the radiopharmaceuticals currently used to treat prostate cancer do not work in a third of patients. The electrons emitted during radioactive decay deliver too small a dose to the smallest metastases or individual tumour cells, so that these are able to survive.

Destroying tumour cells with even greater precision

In PROGNOSTICS, the partners are now testing a drug that uses the isotope terbium-161. This isotope emits electrons with a wide range of energies, including so-called conversion and Auger electrons. Due to their low energies, these have a range of just a few micrometres. They release all of their energy in a cell or in a cluster of cells, making their destructive power more precisely targeted. The tumour cell is damaged, is no longer able to divide and eventually dies, preventing the formation of metastases.

Preclinical studies in mice at PSI have already shown that this is a promising approach. In PROGNOSTICS, the new drug will now be tested at the University Hospital Basel.

The project is benefiting from the development of isotopes at PSI’s large research facilities, led by Nicholas van der Meulen. PROGNOSTICS brings together scientists from the fields of physics, chemistry, biology, pharmacology and medicine who are jointly developing the therapeutic approach from laboratory research to its application in patients. This is not the first time that an interdisciplinary project like this has been successfully implemented, as Schibli points out: “We have shown in the past that we are capable of successfully conducting translational drug research.”

If PROGNOSTICS is successful and the anticipated goals are achieved, further, more extensive clinical trials are planned.