The drug, geldanamycin, is well known for attacking a protein associated with the spread of breast cancer. However, a laboratory-based study found it also degraded a different protein that triggers blood vessel growth.
Stopping unwanted blood vessel growth is a key challenge in the battle against cancer, according to Dr Sreenivasan Ponnambalam, reader in human disease biology in the Faculty of Biological Sciences.
"This is potentially very significant because tumours secrete substances that stimulate blood vessels to develop around them, forming networks that supply nutrients and provide pathways for spread around the body," Dr Ponnambalam said. "This is one of the big problems in cancer: how can we stop the tumour growing and spreading through these blood vessel networks?"
There are already other drugs available that try to stop this growth. One type tries to attack directly the membrane protein VEGFR2, which is essential for new blood vessel growth. However, that approach carries the risk of serious side-effects because proteins in the membrane walls of blood vessels do important work such as controlling blood pressure.
Geldanamycin offers a novel and potentially safer solution because it suppresses the protein indirectly.
The new study, based on experiments with human cells and different animal models, found that geldanamycin indirectly triggered the clearance of the VEGFR2 protein by activating a cellular quality-control system that breaks down many proteins.
That quality-control system already degrades VEGFR2 relatively slowly but the drug accelerates the process, preventing activation of the protein and inappropriate new blood vessel formation.
"With conventional treatments, we have been trying to deal with the situation after the switch has been thrown. What this drug does is destroy the key part of the switch before that switch is thrown," Dr Ponnambalam said.
"Geldanamycin and chemical derivatives have been under intensive study in the laboratory and in clinical trials for the past 20 years. The cost to the NHS or patients could be relatively low compared to the expensive existing anti-cancer drugs, which are still under patent," Dr Ponnambalam added.
The two-year study involved researchers in the University of Leeds and University College London. It was funded by The Wellcome Trust. The paper is published in the journal PLOS ONE.
Steve Clapcote, Jamie Johnston, The Dunhill Medical Trust (Jun 2018), £254,874
Adrian Goldman, MRC (Jun 2018), £98,627
Darren Tomlinson, Michelle Peckham, Megan Wright, BBSRC (Jun 2018), £150,443
Simon Walker, Royal Society (Jun 2018), £337,601
Tom Thirkell, N8 Agrifood (Jun 2018), £14,870
Stephen Muench with Glaxo SmithKline & UCB Celltech, BBSRC Industrial Partnership Award (Apr 2018), £480,225
Steve Clapcote, BBSRC (Apr 2018), £443,072
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
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Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Alison Baker, BBSRC (Feb 2018), £30,000
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
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Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
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Alison Dunn, NERC (Dec 2017), £18,000
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Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
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Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
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