Advancing repurposed drugs to clinical trials for mesothelioma prevention

Qualification: PhD

Department: Cancer Research Centre

Application deadline: 31 August 2020. Interviews in September.

Start date: 11 January 2021

Overview

Supervisor

Project description

Mesothelioma is a type of cancer mainly affecting the lining of the lungs that is linked to asbestos exposure. In some countries, people that have been exposed to asbestos may be offered surveillance, but nothing is actively done to lower their risk of mesothelioma. If a safe and effective therapy was available that could prevent or delay mesothelioma development in exposed high-risk people, this could avoid a huge amount of human suffering and significantly reduce the number of deaths due to mesothelioma.

Safety and tolerability are vital considerations when selecting therapies for cancer prevention. Old generic drugs used for the management of other conditions/diseases that possess good safety profiles make excellent candidates for repurposing as cancer prevention therapies. A major benefit is that existing data can be utilized to rapidly accelerate these drugs into clinical trials, with considerable time and financial savings.

We previously tested 100 generic drugs for ability to inhibit the growth and/or kill mesothelioma cells. We identified a number of promising candidates, including the anti-worming drugs, niclosamide and mebendazole. We also found that niclosamide prevents the growth of human mesothelioma tumours transplanted into preclinical in vivo models. These two drugs warrant testing in a clinical trial to see if they have activity in humans, as a first step towards larger prevention trials. However, before we can progress to trials we need to understand how the drugs are killing mesothelioma cells and identify biomarkers (proteins that are modulated by intervention with the drugs) that can be measured in patient tissues to provide evidence of anticancer activity in humans. The aim of this project is therefore to elucidate mechanisms underlying the protective effects of these drugs, discover new biomarkers and develop methods for their analysis in human tissues. It will utilise state-of-the-art techniques including mass spectrometry-based proteomics, primary explant cultures, and immunofluorescence.

References

  • Neri M et al. (2012) Chemoprevention of asbestos-linked cancers: A systematic review. Anticancer Res. 32, 1005-1013. 
  • Steward WP, Brown K (2013) Cancer Chemoprevention – a rapidly evolving field. Br. J. Cancer 109, 1-7.  
  • Ashburn TT, Thor KB (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov. 3, 673–683. 
  • Pushpakom S et al. (2018) Drug repurposing: progress, challenges and recommendations Nat Rev Drug Discov. doi: 10.1038/nrd.2018.168.  

Funding

Funding

CLS/LPMI/LCRC HOPE PhD studentship for UK/EU Applicants

The Studentship provides:

  • Fees at UK/EU rates for 3 years
  • Stipend (£15,285 per year for 2020/1 – Annual UKRI rate) for 3 years
  • Consumable/Bench fees (£5000 per year)

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in in any biomedical, biochemistry, molecular biology, pharmaceutical or related science or overseas equivalent.  

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

Project enquiries

Application enquiries

How to apply

How to apply

Please use the 'Apply button' at the bottom of the page and select January 2021 entry.

In the funding section of the application please indicate you wish to be considered for the LCRC Brown Jan 2021 Studentship.

In the proposal section please provide the name of the supervisors and project title (a proposal is not required).

With the application, please include: 

  • CV
  • Personal statement explaining your interest in the project, your experience and why we should consider you
  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
  • Evidence of English language proficiency if applicable
  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available.

Eligibility

Eligibility

This funding is available to UK/EU applicants only.