Gene and Oncogene Targeting Team
Team Leader: Professor Caroline Springer
Location: Haddow Laboratories, Sutton
Section: Section of Cancer Therapeutics (including the Cancer Research UK Centre for Cancer Therapeutics)
The research of the Gene and Oncogene Targeting team is two-fold:
Gene targeting
Gene-directed enzyme prodrug therapy (GDEPT) aims to avoid the serious side effects of conventional chemotherapy by converting relatively non-toxic prodrugs into cytotoxic drugs selectively at the tumour. The prodrug-activating enzyme carboxypeptidase G2 (CPG2) is targeted selectively to the tumour by a replicating non-pathogenic viral gene vector. The prodrug is thus activated to the cytotoxic drug specifically in the tumour. A large number of prodrugs have been designed from a range of different classes of drugs. Our conditionally replicating adenoviral vector targets a wide range of tumour types, e.g. hepatoma, colorectal carcinoma, head and neck cancer. We have demonstrated systemic efficacy for this system in a range of tumour models and are working with CR-UK to bring this therapy to the clinic, for head and neck cancer in the first instance.
Oncogene targeting
Mutations that cause permanent activation of the enzyme B-RAF are present in 70% of melanomas, 15% of colorectal cancers and a number of other cancers including thyroid and early ovarian cancer. These mutations result in the tumour cell being in a state of continual growth. We have been discovering and developing inhibitors of B-RAF, with selectivity for the mutant form, for use in malignant melanoma and colorectal carcinoma. We have been working in five different chemical series and have found that inhibitors of B-RAF stop cell growth, and induce the cells to self-destruct.Our plan is to select a clinical candidate shortly.
Aims
- To design novel viral vectors for the systemic delivery of the gene for our prodrug converting enzyme, CPG2. Following expression of the CPG2 we will optimise delivery of our prodrugs to yield efficacy of GDEPT in a range of different tumour models.
- To study the mechanism of action of novel therapeutic compounds that target the RAS/RAF/ERK pathway (in collaboration with Professor Richard Marais).
In the Section of Cancer Therapeutics (including the Cancer Research UK Centre for Cancer Therapeutics)
