DUBLIN CHEMISTS have converted a compound normally used in plastics manufacture into what could prove a very powerful anti-cancer drug. If all goes to plan, this compound, titanocene Y, could become the first successful chemotherapy agent against advanced kidney cancer.
The latest results from the research team at University College Dublin reveal that the compound doesn't just slow tumour growth, as indicated in previous tests - it dramatically shrinks existing tumours as well.
If kidney cancer is diagnosed early enough, patients can be treated surgically and don't progress to needing chemotherapy, according to the Irish Cancer Society. But treatment options for cancer in the advanced stages are very limited, it says. About 140 people in Ireland die every year from the condition, and about 100,000 die globally each year.
The new compound is based on titanocene dichloride, a compound that has been used for many years in the manufacture of polystyrene. This material is used to make licence plates, plastic cutlery, CD cases and other products.
Although scientists knew in the 1990s that titanocene dichloride could kill cancer cells, tests were disappointing. A team led by Matthias Tacke at the School of Chemistry and Chemical Biology at University College Dublin found that by making simple substitutions, they could make the molecules more soluble, and more easily delivered to cancer cells. "Basically, we took a compound used for one purpose and found that there was more to it," Tacke says. He has just completed a series of international conferences in which he presented his latest results. His team has shown their lead compound, titanocene Y, can shrink breast cancer tumours by up to a third in mice.
"This is the first time we have seen shrinkage and, in that regard, it is a bit of a breakthrough," says Tacke. "Although breast cancer is not our target application, the fact that there are such good animal models and that breast cancer is a slower growing tumour meant that we could do more comprehensive testing over longer periods of time. It is an important proof of concept."
Tests also showed that even at the maximum tolerated dose, titanocene-Y exhibits limited toxicity. "The mice do lose about 15 per cent of their weight, but this is not life-threatening and is reversible," says Tacke. By contrast, commonly used chemotherapy agents, such as Cisplatin, which contain platinum, cannot be given to patients with advanced kidney cancer. They are toxic to the diseased kidney, and likely to kill. In earlier tests, titanocene Y merely slowed tumour growth.
The team, based in the Centre for Synthesis and Chemical Biology funded under the Programme for Research in Third Level Institutions, is already working on a new molecule, oxali-titanocene Y, that is 13 times more powerful against cancer cells. New test results are expected soon.