Fully-funded PhD studentships at The Institute of Cancer Therapeutics Doctoral Training Centre - Novel prodrug anti-metastatic therapy for neuroblastoma

This is one of three new fully-funded PhD studentships in the new Institute of Cancer Therapeutics Doctoral Training Centre (ICT-DTC) at the University of Bradford. Focused on the generation of new anticancer prodrugs, the ICT-DTC has been created following a major £2m investment by ICT spin-out company Incanthera Ltd.

We are now looking for applications from outstanding potential PhD candidates.

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Project

Novel prodrug anti-metastatic therapy for neuroblastoma.

Background

Neuroblastoma is a paediatric cancer with a desperate need of new non-toxic therapies to combat relapse, which occurs in 50-60% of children, despite an initially good response to chemotherapy and surgery. Current treatments to prevent and/or treat relapse lack efficacy in some patients, and cause significant side-effects.

We previously demonstrated that cytidine monophosphate (CMP) inhibits polysialyltransferase, the enzyme that regulates biosynthesis of polysialic acid on neuroblastoma cells, promoting tumour migration, invasion and metastasis. CMP, while an effective inhibitor, lacks potency due to very poor tumour cell penetration and in vivo instability.

Aim

To develop a new type of non-toxic prodrug therapy for neuroblastoma, which will inhibit tumour spread (metastasis)

Focus

Synthesis of novel prodrugs of CMP, using clinically proven technology, to address these shortcomings. Evaluation of prodrug stability in blood, neuroblastoma cell penetration and subsequent prodrug release, and effects on tumour cell polysialylation, migration and invasion. Pilot pharmacokinetics study in mice for most promising compound. 

Relevant papers

• Falconer, R.A. et al., Current Cancer Drug Targets, 2012, 12, 925-939
• Al-Saraireh, Y.M.J et al. PLoS ONE, 2013, 8, e73366