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Killing cancer cells with only limited side effects

A group of clinical researchers at the University Hospital in Ulm has discovered new ways to specifically kill cancer cells with radioactive irradiation while preventing healthy organs from being affected. The researchers have also discovered that this method breaks the chemoresistance of cancer cells.

The goal of the researchers was to develop new therapies for the treatment of leukaemias and neuroendocrine tumours using radioactive substances and turn them into practical applications. The method involves binding radioactive substances to messenger substances (in this case, thymidine analogues, or antibodies), which then selectively kill the tumour cells in the cancer-affected regions of the body.

This sounds rather simple, but is in reality quite complicated. The therapy required medical doctors, biologists, chemists and physicists at the Departments of Nuclear Medicine (spokesperson: Prof. Dr. Sven Norbert Reske), Internal Medicine I and III, Paediatrics and Adolescent Medicine at the University Hospital of Ulm and numerous other institutes to work closely together in order to devise a plan that actually worked.

A specific ‘transporter’ needs to be combined with specific irradiation

Professor Sven Norbert Reske (Photo: University Hospital Ulm)

The secret of the method is to bring together the right messenger substance with the right type of irradiation. "We have been able to show that certain substances (e.g., thymidine, which is the DNA nucleoside that pairs with deoxyadenosine) or CD45 antibodies), are excellent messengers for a particular type of irradiation (Auger electron emitters or alpha emitters). The irradiation stops the proliferation of certain cancer cells and activates apoptosis pathways to destroy specifically those cells that do not react to chemotherapeutics," explained Sven Norbert Reske, spokesperson of the group of researchers. "This has previously not been possible with other methods."

The therapy with antibodies has, in the meantime, been used for the treatment of several hundred cancer patients for whom this therapy was deemed appropriate.

Transport into the bone marrow with a radioactive load

The efficient treatment of leukaemias requires the radio-labelled antibodies to reach the bone marrow. However, they might also target the liver and other valuable organs. "To prevent the radio-labelled antibodies from damaging areas not affected by the targeted cancer, the patients are exposed to non-radio-labelled transporters for a certain period of time. As a result, the radio-labelled transporters, when administered at a later time, are diverted into the bone marrow," said Professor Reske, outlining the method.

"When radio-labelled transporters are used later, they will not target the liver and other healthy organs, but most of them will instead head straight towards the bone marrow where they will destroy the leukaemia cells."

The Ulm researchers have developed a new method with which they are able to calculate the length and dose for each individual patient. "This is a promising therapeutic approach for selectively killing tumour cells with limited side effects; it reduces the risk of overdosing and increases the efficiency of leukaemia treatment," said Reske, convinced about the efficiency of the method.

The project, run by the group of clinical researchers at the University Hospital in Ulm, received funding of 1.6 million euros for a period of three years, provided in equal parts by the German Research Foundation (DFG) and the University of Ulm.

Source: University Hospital Ulm (19 December 2008, P, wp)

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/killing-cancer-cells-with-only-limited-side-effects