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Highlights of 2004
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The opening of the Oak Foundation Centre to patients in advance
of the formal opening in February 2005 represents a major landmark
for new drug development at the Royal Marsden/Institute of Cancer
Research.
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Publication of our Phase I clinical trial with the first-in-class
inhibitor of the Hsp90 molecular chaperone 17AAG in the Journal
of Clinical Oncology. This includes the first demonstration of
molecular target inhibition in the tumour and of prolonged stable
disease in 2 patients with metastatic melanoma, leading to a Phase
II trial in this disease.
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In collaboration with Vernalis, our discovery of nanomolar inhibitors
of Hsp90, exemplified by publication of VER-49009, led to a licensing
agreement with Novartis for their further development.
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In collaboration with PIramed Ltd we have identified a development
candidate from our potent and selective inhibitors of PI3 kinase
and plan to initiate Phase I trials around the end of 2005. A
series with oral bioavailability has also been identified.
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Based on promising preclinical results, a proposal for a GDEPT
Phase I clinical trial has been accepted by Cancer Research UK
New Agents Committee.
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Discovery of nanomolar inhibitors of PKB, in collaboration with
Astex Technology Ltd, and demonstration of activity in human tumour
xenograft models.
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In collaboration with Dr R Marais, Professor D Barford and Astex
Technology Ltd, a 20nM inhibitor of mutant B-RAF has been identified.
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We have continued to exceed our goal of running six high throughput
screens per year, with promising hits emerging against several
new targets.
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We have identified novel inhibitors that show differential effects
on HIF-1 activity in response to growth factors and hypoxia.
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As an example of new targets, a screen to identify inhibitors
of the SET 7/9 histone methyltransferase is in progress.
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