April 7, 2006
CSCB researchers discover potential chemotherapy agent for treating kidney cancer

Each year in excess of 100,000 people worldwide die from renal cell cancer, which is the most common type of kidney cancer. In Ireland alone, 266 new cases and 140 cancer deaths are reported per year.1

Renal cell cancer can be treated in a number of ways depending on the stage of the cancer and the patient's age and health. Early detection is key in treating it successfully with surgery but if the cancer reaches an advanced stage, removal of a kidney is often necessary. Renal cell cancer can be treated with radiation, but this cancer has proved to be very resistant to chemotherapeutic drugs so far.

Dr Matthias Tacke, a Senior Lecturer at the UCD School of Chemistry and Chemical Biology and a researcher with the Centre for Synthesis and Chemical Biology has been working on known anti-cancer drugs belonging to the titanocene family for five years.

"Titanocene dichloride is a cytotoxic anti-cancer drug, which means that it can selectively kill cancer cells. However, in Phase II clinical trials carried out in Germany in 1998 titanocene dichoride was found not to be cytotoxic enough to justify further trials," explains Dr Tacke. "We decided to focus our research in UCD on making derivatives of titanocene dichloride, which we hoped would be more efficacious."

The research resulted in Dr Tacke's group synthesising 25 novel compounds in the lab, which were structurally identified and then biologically evaluated.

"Results from the in vitro testing of these compounds were really encouraging. Our best novel compound proved to be 100 times more cytotoxic than titanocene dichloride itself, which was administered in those early clinical trials," continues Dr Tacke.2

The next stage for Dr Tacke and his collaborators was to carry out in vivo studies in mice bearing a human form of renal cell cancer. These in vivo experiments proved that their best compound significantly reduced tumour growth and the results were superior when compared to Cisplatin, which is an established chemotherapy against a variety of cancers.3

The in vivo toxicity testing of Dr Tacke's optimal compound shows a very promising profile: it is not very toxic for the liver and kidneys, does not interfere with the blood formation and activates the immune system instead of weakening it like most other anti-cancer drugs.

"Our research is aimed at promoting a further improved titanocene into a clinical Phase I study against renal cell cancer in the near future," concludes Dr Tacke. "This could mean that we are on our way here in Ireland to finding an improved chemotherapy product for treating renal cell cancer."



Publications referenced
1The National Cancer Registry Ireland. Incidence, mortality, treatment and survival 1994-2001.

2Sweeney, N. J.; Mendoza, O.; Müller-Bunz, H.; Pampillón, C.; Rehmann, F-J K.; Strohfeldt, K.; Tacke, M. Novel benzyl substituted Titanocene anti-cancer drugs. J. Organomet. Chem. 2005, 690, 4537-4544.

3Fichtner, I.; Pampillón, C.; Sweeney, N. J.; Strohfeldt, K.; Tacke, M. Anti-tumour activity of Titanocene Y in xenografted Caki-1 tumours in mice. Anti-Cancer Drugs 2006, 17, 333-336.


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