Bioscience for an integrated understanding of health

Category: Standard Studentships

Developing SSAs for the treatment of Bladder Cancer

Project No.2217

Primary Supervisor

Prof Michelle Garrett – University of Kent

Co-Supervisor(s)

Dr Jennifer Hiscock – University of Kent

Dr Tim Fenton – University of Southampton

Mr Sashi Kommuclinician – (Clinician, surgeon), Department of Urology, East Kent Hospitals University NHS Foundation Trust

Summary

Bladder cancer kills over 5,000 people per year with 10-year survival being less than 50%.

Treatment combines surgery with chemotherapy, chiefly mitomycin or gemcitabine delivered via catheter directly to the bladder. The effectiveness of these agents is limited by their ability to be taken up by the cells of the bladder.  
 
Supramolecular Self-associating Amphiphiles (SSAs) are a new class of molecule invented by JH, and in collaboration with MG have been shown to act as anticancer agents and enhancers of anticancer agent efficacy. This project will provide proof of concept for the use of SSAs to increase the efficacy of mitomycin/gemcitabine and provide a route to proof-of concept clinical trial for SSAs in bladder cancer. 
 
Aims: 
1. Synthesis of a selected set of SSA’s for analysis on bladder cancer cell   
     lines. 
2. Evaluate anticancer activity and membrane interactions of SSAs on    
    bladder cancer cell lines. 
3. Investigate potential correlations between gene expression (RNA Seq) of      
    bladder cancer cell lines with SSA activity. 
 
Output:  
Preclinical proof-of-concept of therapeutic efficacy of SSAs for treatment of bladder cancer. 
 
Scientific approach:  
JH Lab: 
*   Synthesis and design of SSAs (Aims 1, 2). 
*   Evaluate the physicochemical effects of SSAs (Aims 1, 2). 
*   Perform patch clamp, membrane fluidity and vesicle leakage experiments  
      to ascertain SSA interaction with model cell membranes (Aims 1, 2). 
 
MG lab:  
*   Evaluate cell cytotoxicity for SSAs alone/in combination with    
     mitomycin/gemcitabine on bladder cancer cell line panel (Aim 2).  
*   Perform detailed cell membrane interaction studies including confocal  
      microscopy and electron microscopy (Aim 2). 
 
TF Lab: 
*    RNA sequencing of bladder cancer cell lines to investigate correlation of      
      gene expression patterns with SSA effects i.e. enzymes that alter   
      membrane composition (Aim 3). 
 
SK (clinician/surgeon):  
*    Clinical expert in Bladder Cancer to guide project success towards the    
      clinic (Aims 1-3).