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New therapeutic approaches for lymph node cancer

(Vienna, 31 August 2010) In a cooperation project between MedUni Vienna and the Salzburg University Hospital it has now been possible to prove that recently discovered molecules in the genetic material have a decisive influence on the development of lymph node cancer. This finding puts the therapeutic use of these molecules within reach. The scientific work is therefore also being published in the current issue of the specialist magazine of the American Academy of Sciences (PNAS).

A team of researchers headed by Dr. Olaf Merkel, Salzburg University Hospital, and Ao. Univ. Prof. Dr. Lukas Kenner, Medical University of Vienna, has for a while been dealing with highly-malignant lymphomas (malignant tumours of the lymph nodes) which also often occur in children. Typical of lymphomas is the pathological link of chromosomes to combine genes that are otherwise not connected together into a hybrid protein molecule. In the tumours these hybrid protein molecules lead to massive activation of the control element "ALK", which normally conveys growth signals. Overactivation of "ALK" leads to the multiplication and degeneration of white blood cells (so-called lymphocytes), however, and therefore causes cancer. But in around 50% of lymphoma patients the described "ALK" hybrid molecules are missing, which was unable to be explained sufficiently before.

The group of researchers has now found out that very small, only recently discovered molecules in the genetic material – so-called microRNAs – are responsible for this. These microRNAs control the production of a large number of protein molecules within a cell and have a lasting effect on growth behaviour.
The team has been able to show that in the case of tumours with "ALK" the carcinogenic microRNA 17-92 exists to a much higher extent than in patients without the "ALK" hybrid molecule, while the microRNA-155 in ALK-negative patients exists in quantities which are more than 10 times higher. Overactivity of microRNA-155 also leads to tumours in mice. Activation of microRNA-101, however, also leads to reduced growth of cancer cells.

"This opens up new treatment options. The inhibition of one of the target molecules of the microRNA-101 (mTOR protein), for example, was able to clearly reduce tumour growth. The direct or indirect use of microRNAs for therapeutic purposes in humans is therefore within reach. With the stability of the small microRNA molecules and their relatively easy handling microRNAs are very interesting target molecules for therapy, and with these it may also soon be possible to develop innovative therapeutic agents against these highly malignant tumours," says Kenner, explaining the result of the research.

This work is also being published in the current issue of the specialist magazine of the American Academy of Sciences, Proceedings of the National Academy of Sciences (PNAS):

» Identification of differential and functionally active miRNAs in both anaplastic lymphoma kinase (ALK)+ and ALK- anaplastic large-cell lymphoma
Olaf Merkel, Frank Hamacher, Daniela Laimer, Eveline Sifft, Zlatko Trajanoski, Marcel Scheideler, Gerda Egger, Melanie R. Hassler, Christiane Thallinger, Ana Schmatz, Suzanne D. Turner, Richard Greil and Lukas Kenner
doi: 10.1073/pnas.1009719107