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German Cancer Prize 2005 goes to Prof. Claus Scheidereit (MDC) and Prof. Bernd Dörken (Charité) – Molecular Basis of Hodgkin’s Lymphoma Decoded

Prof. Claus Scheidereit from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Prof. Bernd Dörken (Charité – University Hospital Berlin, Campus Berlin-Buch, Campus Virchow and the MDC) have been awarded the German Cancer Prize 2005 for deciphering the molecular mechanism of Hodgkin’s lymphoma, a common cancer of the lymphatic system. The award was presented to them at the Congress of the German Cancer Society on March 14, 2005 in Würzburg. The researcher and the clinician have “contributed significantly to the understanding of the molecular causes of Hodgkin’s lymphoma with their excellent research work, which was in part done in close cooperation, and have thus enabled the development of new therapeutic approaches”, as was stated in the announcement of the award. The German Cancer Prize goes to researchers from the MDC and clinicians from the Charité for the second time. In 1999 Prof. Walter Birchmeier (MDC) and Prof. Peter M. Schlag (Charité – Campus Berlin-Buch and MDC) received this award. Since its founding in 1992, the MDC, an institution of the Helmholtz Association, has worked closely with clinicians of the Charité. One main scientific focus at the MDC is cancer research.

Hodgkin’s lymphoma is one of the diseases of the lymphatic

system and is accompanied by a swelling of the lymph nodes (part of the immune

system), fever, night sweats, and weight loss. The disease is named after the

British pathologist Thomas Hodgkin (1798-1866), who first described the disease

in 1832. Characteristic of the disorder is the presence of mononucleated

Hodgkin cells and giant, multinucleated Reed-Sternberg cells in the lymph

nodes. The exact processes involved whereby healthy white blood cells become

malignant are not known. Until a few years ago, it was also unclear which

molecular mechanisms contribute to the development of this cancer of the lymph

glands.

However, in 1996 Prof. Scheidereit and Prof. Dörken

discovered the gene switch NF-kappaB in the nuclei of the Hodgkin

Reed-Sternberg cells of Hodgkin patients. It became evident that this gene

regulator triggers the malignant cell growth in Hodgkin’s lymphoma. NF-kappaB belongs to a group of gene regulators

that transmit signals, such as in virus infections or inflammatory processes.

These NF-kappaB factors normally lie dormant in the interior of the cell

(cytoplasm), retained by the so-called inhibitor proteins (IkappaB). Following

bacterial or viral infection, messenger substances of the immune system, the

so-called cytokines, activate NF-kappaB factors and temporarily send them into

the cell nucleus. There, NF-kappaB factors switch on certain genes whose

products, in turn, cause the immune cells to take up a defensive position.

After completing their work, the NF-kappaB molecules leave the cell nucleus and

wander back in the cytoplasm.

In contrast, in the malignantly altered cells of Hodgkin’s

lymphoma, NF-kappa-B is constantly in the cell nucleus. The reason, as the

researchers discovered, is that certain, permanently activated enzymes

(so-called IKKs) switch off inhibitor proteins that normally retain NF-kappaB

in the cell plasma. Furthermore, they were able to show that, in a portion of

the patients, the inhibitors are defective due to mutations. All Reed-Sternberg

cells studied, in which NF-kappaB could be detected in high concentrations in

the cell nuclei, grow uninhibited both in vitro as well as in animal

experiments. These cells are no longer able to trigger the cellular protective

programme which normally leads to apoptosis in wrongly programmed cells. The

researchers managed to stop the malignant growth of the Reed-Sternberg cells by

flushing the NF-kappaB out of the cell nucleus into the cell plasma with an

artificial inhibitor protein that cannot be inactivated by IKK. The gene on/off

switch is thus shackled and can no longer leave the cell plasma. More recently,

using DNA chip technology, Prof. Scheidereit and Prof. Dörken were able to

identify other factors that interact with NF-kappaB and elucidate their

function. As such, they have made a further contribution to the decoding of the

complex signal network of Hodgkin’s lymphoma.

New therapeutic

approaches

Up until now, Hodgkin’s lymphoma was treated with radiation

therapy and chemotherapy. The work of Prof. Scheidereit and Prof. Dörken has

now provided the basis for the development of new therapeutic approaches. In

pre-clinical studies, different substances are currently being tested as to

their capability to directly or indirectly block IKK activity. It remains to be

seen whether this alone will develop into a new and more effective therapy, or

whether these approaches will supplement and improve chemo and radiation

therapy.

Prof. Claus

Scheidereit, born in Schleswig, Germany in 1954, has been Research Group Leader

at the MDC since 1995 and is also Associate Professor at the Free University

(FU) of Berlin. He studied chemistry at the University of Marburg and was a

scientific assistant there after completing his doctoral degree. He completed

his post-doc training at Rockefeller University in New York, USA. In 1988, he

was given his own research group at the Max Planck Institute for Molecular

Genetics (Berlin). In 1992, he completed his post-doctoral

normal'>Habilitation

thesis at the FU qualifying him to become a professor

in biochemistry.

Prof. Bernd Dörken,

born in Siegen, Germany in 1947, is an oncologist, haematologist, and tumour

immunologist. He studied medicine in Erlangen und Nuremberg and was active for

many years at the University of Heidelberg. In 1992, he was appointed as a C4

professor at the Charité in the Rössle Clinic in Berlin-Buch and was Medical

Director there at the Medical Clinic with a focus on haematology, oncology, and

tumour immunology. Since 2001, he has served as the Medical Director of the

Medical Clinic with main focus on haematology and oncology at the Campus

Virchow Klinikum of the Charité. In conjunction with his appointment to

Berlin-Buch in 1992, Prof. Dörken became Research Group Leader at the then

newly founded MDC.

Prof. Claus Scheidereit (MDC) (photo: private)

Prof. Bernd Dörken (Charité - University Hospital Berlin and MDC) (photo: private)

Barbara
Bachtler
Press
and Public Affairs
MaxDelbrück
Center for Molecular Medicine (MDC)
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