Introduction

Research Groups

Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

Service & Research Support Facilities

Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

Past members last known active weblink

Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

Reset Menus

Anti-Angiogenic Strategies in Cancer Therapy

Research Groupings: Cancer | Structural and molecular cell biology

The growth of solid tumours beyond a threshold size (~1 mm dia) requires angiogenesis, the development of new blood vessels. This has focussed attention on anti-angiogenic agents for the treatment of cancers and particularly to inhibit the growth of secondary tumours (metastases).

Fig. 1. Normal (left) and CA-4P-treated (right) human endothelial cells stained for tubulin, showing the disruption of cytoskeletal structure by the drug.

We have recently shown that combretastatin-4P (CA-4P), a tubulin-binding compound (Fig. 1) currently undergoing Phase I clinical trials, not only retards primary tumour growth but is a potent inhibitor of metastasis in mice (Fig. 2). CA-4P also disrupts neovasculature in mouse goitre, a rapidly proliferating, non-tumour tissue. These observations indicate the potential of CA-4P as an anti-metastatic agent and for the treatment of angio-proliferative diseases (e.g. atherosclerosis, diabetic retinopathy). In a complementary anti-angiogenic approach we are developing adenovirus-based targetted gene therapy strategies.

In a parallel programme focussed on transforming growth factor b (TGFb), we have recently identified four novel mutations in the TGFb type 2 receptor in breast tumours from patients who had become refractory to tamoxifen treatment.

Fig. 2. The lungs of mice treated with CA-4P (left) show few metastases from a subcutaneous primary tumour compared with the lungs of untreated mice (right) and resemble normal lung (centre).

Three of these mutations greatly impair the signalling function of the receptor. These findings establish a rationale for a systematic analysis of components of the TGFb signalling pathway for mutations that may contribute to the development of tamoxifen resistance.

References