Belgian researchers explore revolutionary approach to an...( e a an endolthelin antagonist in this ...)

e a an endolthelin antagonist in this case a cyclic peptide called BQ123 to target selectively one of the ET receptors, ET-A, that we found was particularly dense in the tumour arterioles. This peptide completely wiped out the ability of the arterioles to contract and kept them wide open. We were able to demonstrate, using laser doppler probes and imaging that this increased blood flow to the tumour but that healthy tissue was not affected. We were then also able demonstrate that administering BQ123 could significantly increase the delivery of the anti-cancer drug cyclophosphamide to the tumour. Furthermore, tumour response to fractionated radiotherapy was also improved significantly because the increased blood flow carried more oxygen to the tumour."

Dr. Feron, who is an assistant professor and research associate in the Department of Internal Medicine at the University of Louvain, said that the team was now planning to start Phase I clinical trials in patients. "The chances for this anti-tumour adjuvant therapy to be well tolerated are high as ET-1 antagonists would be used acutely to produce an immediate effect on the tumour blood vessels i.e. given at the same time that the chemotherapy or radiotherapy is administered."

He said that although the research was in mice and that it was early days as the concept still had to be proved in patients, the principle of keeping tumour arterioles open to boost responses to treatment should work in the many tumour types where ET-1 was expressed.

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Contact: Margaret Willson
m.willson@mwcommunications.org.uk
41-227-612-211
European Organisation for Research and Treatment of Cancer
30-Sep-2004

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