February 4, 2008
UCD scientist makes an advance against cancer cells

Dr Matthias Tacke and his research team at the CSCB and UCD School of Chemistry and Chemical Biology have recently published highly significant preclinical results on the anti-tumour activity of Titanocene Y on human breast tumours and in a mouse model.

Titanocenes are a novel series of promising anti-tumour agents. In the research team's recent studies on a mouse model, a decrease not only in tumour growth, but also a reduction in tumour volume, was observed for the first time. Titanocene Y caused a reduction in breast cancer tumours by around one-third of their volume.

In the human breast cancer, Titanocene Y showed cell death induction comparable to the widely-used chemotherapy drug Cisplatin. It has also been successfully applied to kidney cancer, which is unreceptive to most chemotherapy. Finding a chemotherapy drug against this form of cancer is difficult because of the kidney's attempts to filter out the drugs sent in to kill the cancer. Some drugs may also trigger unwanted inflammation of the organ or even organ death.

Dr Tacke and his team of chemists have designed these metal-based compounds called titanocene dichlorides. He and his collaborators have then transplanted human kidney cancer into immune deficient mice and then treated them with the investigational drugs. The compound is dissolved and injected into the blood of the mouse. It finds its way to the cancer cells automatically - due to information inbuilt into the molecule. The cancer cells take up the compound and die. They are poisoned selectively inside the mouse.

"Our compounds have gone through four rounds of optimisation and we can now shrink tumours in mice," said Tacke. "The good news is the toxicity seems to be limited in the healthy cells so it's not too toxic to the rest of the body. We see a very good effect on breast tumours as well. The human tumours have been shrinking in the mouse models."

The researchers are also working on drugs designed to treat other cancers including prostate, ovarian and cervical cancer. "We have developed compounds but they are not as far advanced as the one we have tested in the breast or kidney cancer models. The successor molecule to Titanocene Y has been synthesised and has been shown to be 13 times more cytotoxic in vitro," says Dr Tacke.

He hopes clinical trials with Titanocene Y on humans, the next stage of the testing process, could happen in three to five years.

Reference:
Beckhove, P., Oberschmidt, O., Hanauske, A. R., Pampillon, C., Schirrmacher, V., Sweeney, N. J., Strohfeldt, K., Tacke, M. Anti-Cancer Drugs 2007, 18: 311-315.


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