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How to make tumour cells undergo suicide?

The pathologist Dr. Wilfried Roth was awarded the Rudolf Virchow Prize for his work on inducing apoptosis in tumour cells.

Wilfried Roth, MD, Institute of Pathology, Heidelberg University © University Hospital Heidelberg

What kind of molecular messages can make tumour cells undergo apoptosis? Researchers at the Institute of Pathology at the University Hospital of Heidelberg and the German Cancer Research Centre (DKFZ) have deciphered signalling chains that affect the tumour cells' apoptosis programme and that might open up new strategies for therapies.

Dr. Wilfried Roth, head of a junior researcher group at the DKFZ and the Institute of Pathology, was awarded the Rudolf Virchow Prize with its accompanying cheque of 5,000 euros. The award was presented at the Annual Meeting of the German Society of Pathology, held from 4th to 7th June 2009 in Freiburg.

The miracle word: apoptosis 

Under normal circumstances, all cells have a programme that induces their death (apoptosis) under certain conditions. A smart method of removing tumour cells from the body centres on the possibility of sparking off this suicide programme. The molecular mechanisms of apoptosis are highly complex and can be defective in many locations. Tumour cells are constantly developing numerous strategies to avoid undergoing cell death.

Positions in the Institute of Pathology and the DKFZ

Wilfried Roth worked on apoptosis while he was doing his doctoral thesis. During a research stay at the Burnham Institute, San Diego, USA, for which he had a grant from the German Research Foundation, Roth was able to gain further insights into apoptosis. He has been a scientist at the Institute of Pathology at the University Hospital of Heidelberg (Medical Director: Professor Dr. Peter Schirmacher) since 2004 where he also habilitated. Besides his work as chief physician, the outstanding 39-year-old researcher has been head of a Max Eder junior researcher group funded by German Cancer Aid at the German Cancer Research Centre since 2005.

“Research is of course all about teamwork,” said Wilfried Roth, “and because my application for the Virchow Award involved several publications, it goes without saying that numerous people’s work has contributed to these research results.” His staff members work in the Institute of Pathology as well as in the German Cancer Research Centre.

New therapies arise from the interference with the signalling chains

Roth and his team of researchers are working on the discovery of decisive regulatory steps in the mechanisms that lead to cell death in order to target the growth of tumours with new drugs. Each type of tumour might be defective at a different step. For example, brain tumours produce a protein that inhibits cell death. This makes therapy very difficult. If the production of this protein can be prevented, then the cell death cascade could once again become active.

Kidney tumours have a larger quantity of a receptor that induces apoptosis. Roth and his team see this as an opportunity to target this death receptor with drugs, which would make tumour therapy far more effective.

Significant prognosis factors to determine therapies

Patients with a severe form of cancer might be able to benefit from additional, partially new therapies. Independent prognostic factors assist in the decision to use such adjuvant therapy studies. In kidney tumour patients, Roth’s team of researchers identified factors in the apoptosis signalling chain that might indicate the course of the disease and the mortality of the patients affected: the protein DcR3 (decoy receptor 3) binds and inactivates a second messenger that induces apoptosis. DcR3 can be determined in the blood. High DcR3 levels suggest an unfavourable prognosis. Similar findings have been obtained for a death receptor and the secondary messenger that binds to it, whose presence in tumour tissue is currently being investigated.

Rudolf Virchow Prize: Top award for pathologists

The Rudolf Virchow Prize is named after the founder of pathology. The prize has been awarded by the German Society for Pathology every year since 1980 to a pathologist under 40 years of age. It is the top award given to pathologists in Germany.

Further information:
PD Dr. med. Wilfried Roth
Institute of Pathology
University of Heidelberg
Im Neuenheimer Feld 220/221
69120 Heidelberg
Tel.: +49 (0)6221 / 56-26 47
E-mail: Wilfried.Roth(at)med.uni-heidelberg.de

or:
Molecular Neuro-Oncology
German Cancer Research Centre (DKFZ)
Im Neuenheimer Feld 280
69120 Heidelberg

Literature:
Macher-Goeppinger S, Aulmann S, Tagscherer KE, Wagener N, Haferkamp A, Penzel R, Brauckhoff A, Hohenfellner M, Sykora J, Walczak H, Teh BT, Autschbach F, Herpel E, Schirmacher P, Roth W Prognostic value of Tumor Necrosis Factor-Related Apoptosis-inducing ligand (TRAIL) and TRAIL receptors in renal cell cancer. Clinical Cancer Research 15, 650-659, 2009.

Tagscherer KE, Fassl A, Campos B, Farhadi M, Kraemer A, Boeck BC, Macher-Goeppinger S, Radlwimmer B, Wiestler OD, Herold-Mende C, Roth W Apoptosis-based treatment of glioblastoma with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene 27, 6646-56, 2008.



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