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Cilengitide could promote tumour growth

UK scientists have found that a type of angiogenesis inhibitor currently under development for use in the treatment of cancer can actually encourage rather than inhibit tumour growth when administered at low doses

UK scientists have found that a type of angiogenesis inhibitor currently under development for use in the treatment of cancer can actually encourage rather than inhibit tumour growth when administered at low doses.

A multi-centred study was carried out on Merck KGaA's cilengitide, a type of angiogenesis inhibitor that targets integrins, ie receptors on the surface of cells that play a number of roles, including defining cellular shape, mobility and regulating the cell cycle. In preclinical trials, blocking the action of integrin inhibits the angiogenesis process, ie the growth of the new blood vessels that a tumour needs to survive and grow. This action has made them an attractive target for potential drug therapy. However they have not proved as successful in human clinical trials as had been hoped, and it was this anomaly that the study hoped to address. 

The study showed that cilengitide can act to promote cell growth and blood vessel formation instead of blocking it. This is because the angiogenesis changes the way that integrin and VEGF receptors move inside blood vessels. It was suggested that this could be a previously unknown characteristic of drugs similar to cilengitide.

Dr Lesley Walker, director of cancer information at Cancer Research UK says: "This may help to explain the mixed results previously seen in patients and turn around disappointing results so people may still benefit from the drug without the potential harm."

"Other anti-angiogenesis drugs like sunitinib (Sutent) and bevacizumab (Avastin) have proven effective enough for use in the NHS but there is still need to understand why they can sometime fail. It may be that there are similar mechanisms at work," she said.

Several other integrin inhibitors are currently in clinical trials. Cilengitide is the furthest advanced, in Phase III trials, and two monoclonal antibodies are in Phase II.

Results of the cilengitide study were published in the March 22 online issue of Nature Medicine.

23rd March 2009

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