Dr Sue Eccles

Our research focuses on cellular processes involved in invasion and metastasis and their potential to yield new molecular therapeutic targets. We have a particular interest in glioma, prostate cancer and squamous carcinomas of the head and neck. We have established a comprehensive portfolio of assays of angiogenesis, invasion and metastasis for target discovery/ validation and evaluation of novel inhibitors emerging from the Division of Cancer Therapeutics’ drug discovery programme.

For practicality and efficiency we mainly utilise molecularly characterised human tumour xenografts, and are further expanding our collection of those derived direct from clinical material. We favour orthotopic or metastatic models and have shown that these can provide more clinically-relevant results (such as in Wilms tumour, with Chris Jones). We have developed the first paediatric orthotopic glioma models (with Lara Perryman) which, together with transgenic models of medulloblastoma and neuroblastoma developed by Louis Chesler, will be invaluable for collaborative projects focussing on paediatric drug development.

Many of the tumour models have been engineered to express luciferase for both bioluminescent imaging of tumours and to measure intracellular signalling using reporter assays. We also work closely with Simon Robinson (MRI) and Mounia Beloueche-Babari (MRS) to measure the effects of genetic manipulation or targeted agents on tumour physiology and metabolism.

Our research has contributed to the nomination of several molecularly targeted anti cancer agents that are now in preclinical development or clinical trial (for example HSP90, PI3K, PKB, HDAC, CDK, alpha-FR) or in late Lead Optimisation (Aurora, CHK1). Current projects in our preclinical portfolio include PPM1D, MAP4K4, Wnt and HSF-1.

We have also focused on developing a suite of high-throughput microplate 3D functional assays to bridge the gap between simple monolayer assays of tumour growth and survival and in vivo tumour models and to address the key aspects of tumour progression exemplified by invasion and angiogenesis.

Aims

• Targeting key signalling pathways in tumour and host cells which potentiate angiogenesis and metastasis.
• Preclinical development of novel targeted therapies and an understanding of microenvironmental mechanisms of resistance.