Professor Caroline Springer PhD FRSC
Academic Title: Professor of Biological Chemistry
Team: Gene & Oncogene Targeting
Tel: 0208 722 4214
Location: Haddow Laboratories, Sutton
Professor Springer leads research in the following areas:
1. Development of novel inhibitors to treat mutant BRAF-driven tumours.
2. Development of gene-directed enzyme prodrug therapy (GDEPT) to the clinic.
3. Design and development of LOX inhibitors as anti-invasive and anti-metastatic drugs.
We are a multidisciplinary team, comprising biochemists, chemists and pharmacologists. We have received funding from Cancer Research UK and the Wellcome Trust and focus on medicinal chemistry to develop new cancer therapies.
1. We have designed and synthesised novel mutant BRAF kinase inhibitors and co-crystallised many of them with BRAF. In addition we developed a screening cascade for the identification of oral inhibitors of mutant BRAF with therapeutic efficacy in melanoma and colon xenograft models. Three preclinical candidates were nominated and are currently in preclinical evaluation with the aim of progressing one candidate drug though to Phase I clinical trials in the The Royal Marsden NHS Foundation Trust funded by the Wellcome Trust.
2. We have been funded by Cancer Research UK to develop a targeted therapeutic suicide gene therapy approach called GDEPT (gene-directed enzyme prodrug therapy) aimed at reducing the toxic side-effects associated with conventional chemotherapy. We have demonstrated systemic and intra-tumoral efficacy in a range of human xenograft models, (including colorectal carcinoma, hepatoma, and head and neck cancers), using an engineered adenoviral vector. A clinical trial of our GDEPT therapy in the The Royal Marsden NHS Foundation Trust, for use in head and neck cancer patients, is being funded by Cancer Research UK.
3. Recently we have been awarded funding by Cancer Research UK and the Wellcome Trust to work on the enzyme lysyl oxidase (LOX) which plays a critical role in the metastatic spread of tumours. We aim to develop selective low molecular weight drugs to inhibit LOX in patients for effective treatments in metastatic disease. Several hit series of LOX inhibitors were discovered by high throughput screening, and the most active series are currently in lead optimisation.
Professor Caroline Springer leads a multidisciplinary team called Gene and Oncogene Targeting within the Division of Cancer Therapeutics at The Institute of Cancer Research (ICR). Her work focuses on the discovery of a wide range of novel therapeutics.
After completing her PhD in biological chemistry at University College London, Professor Springer began work at the ICR on the novel ADEPT (antibody-directed enzyme prodrug therapy) treatment designed to target tumours selectively. The target tumour was colorectal carcinoma and this work led to four ADEPT clinical trials at Charing Cross, Royal Free and University College London Hospitals in London.
Professor Springer developed gene-directed enzyme prodrug therapy (GDEPT), a suicide gene therapy treatment that can be used in a wide range of cancer types. This work is now coming to fruition clinically with a Cancer Research UK sponsored GDEPT clinical trial in head and neck cancers, scheduled to start in The Royal Marsden NHS Foundation Trust, London, in 2012.
Professor Springer is currently investigating several different therapeutic approaches with Cancer Research UK and Wellcome Trust funding. Recently, this has included research into lysyl oxidase inhibitors, an enzyme that is important in invasion and metastasis. The goal is to prevent and treat metastases in a range of tumour types. This work is in collaboration with Professor Richard Marais and Dr Janine Erler.
Four series of LOX inhibitors were developed following a large high throughput screen and work has begun in lead optimisation with two series of inhibitors.
A key area of research has been to discover inhibitors of mutant BRAF, which will be used for treatment for some types of melanoma and colorectal cancers. This work is in collaboration with Professor Richard Marais.
Two preclinical BRAF candidates have recently been selected and work is ongoing to select the best one to take forward for a melanoma clinical trial at The Royal Marsden Hospital.