Targeted Platinum-based Chemotherapy for the Treatment of Neuroblastoma
Project details
First supervisor: Professor Mahvash Tavassoli
Second supervisor: Professsor Stefano Giuliani
Third supervisor: Dr Adam Sedgwick
Sponsor: Cancer Research UK
CYP PhD recruitment process – CRUK – City Of London Cancer Centre (colcc.ac.uk)
2025 CYP PhD project Tavassoli – CRUK – City Of London Cancer Centre (colcc.ac.uk)
Funding available: Stipend £23,000 per annum (current CRUK rate), plus consumables (approximately £15,000 per annum)
Duration of award: 4 years
Mode of study: Full time
Eligibility: Home, EU and overseas. Tuition fees paid for Home fee status only.
Start date: September 2025
Application deadline: 5 November 2024, 12:00
Reference number: 2024/10/MT/DOCS
Project description
Hypoxia (low oxygen) is a common characteristic of most solid tumours. Exploiting tumour hypoxia to convert a “non-toxic” prodrug into the active toxic counterpart has the potential to afford a cancer selective therapeutic and overcome the dose limiting effects of traditional chemotherapy. Within most solid tumours, there are regions of hypoxia (low oxygen levels) due to the increased metabolic demand of cancer cells and poor tumour vasculature. The severity of hypoxia can vary between tumour types.
Importantly, several studies in a range of tumour types have demonstrated that hypoxia correlates with poor patient prognosis and increased tumour aggressiveness, therefore making tumour hypoxia a key therapeutic target within oncology. The significant differences in oxygen levels between tumour and healthy tissue provide an avenue to exploit for the development of a cancer-selective therapy.
We have shown that hypoxia plays an important role in treatment resistance of head and neck cancers. In this project we propose to develop hypoxia-mediated activation of Pt(IV) prodrug into the active toxic Pt(II) counterpart. Several hypoxic cancers are treated with a Pt(II) chemotherapy; therefore by designing a HAPt, we have the potential to selectively deliver the beneficial therapeutic properties of Pt(II) while overcoming the dose-limiting off-target toxicity.
Person specification
The candidate is expected to have a first degree in biological sciences, related fields or a medical degree. As the project involves chemical synthesis of probes, knowledge of chemistry would be desirable but not necessary as comprehensive training will be provided in the conceptual and technical aspects.
Research training
Training in basic techniques will be provided by the supervisors including developing the 2D and 3D models. Training in synthesis of the required prodrugs, imaging and related skills will be provided by supervisor (AS). We collaborate with ProfIsmael Díez-Pérez on this project who will provide training in nanochemistry and computational biology. Training in working with neuroblastoma organoid and animal models will be provided by supervisor (SG).
There is a comprehensive training program for PhD students in the participating institutes at King's,UCL,Crick, and other researchers at the COLCC Centre. The students will be actively encouraged to join training workshops in a wide range of laboratory, imaging, statistics, bioinformatics and other transferable skills.
Next steps
Please apply online at the CRUK website
Applicants are strongly encouraged to discuss with the first supervisor prior to submitting an application.
Professor Mahvash Tavassoli
Mahvash.tavassoli@kcl.ac.uk
Related Centre: Centre for Host-Microbiome Interactions
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