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Novel prodrug anti-metastatic therapy for neuroblastoma

  • Full or part time
  • Application Deadline
    Tuesday, April 30, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

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.

Project 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)

Project
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.

Funding Notes

Studentships cover tuition fees, a tax free stipend (at standard MRC rates, £15,009 per annum 2019/20) for the duration programme and writing-up (3.5 years total) and a generous research budget. A travel fund is also provided for each student to guarantee participation in a national and international conference. Funding for specific training courses is also included in the DTC.

References

Entry requirements

At least 2:1 honours degree in Chemistry, Medicinal Chemistry, Pharmacy or related subjects. An MSc in any of these areas is an advantage.
For full details of our entry requirements, please visit our website.

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