Prof Michelle Garrett – University of Kent
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
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 a proof-of concept clinical trial for SSAs in bladder cancer.
1. Synthesis of a selected set of SSA’s for analysis on bladder cancer cell
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.
Preclinical proof-of-concept of therapeutic efficacy of SSAs for treatment of bladder cancer.
* 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).
* 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).
* 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).
* Clinical expert in Bladder Cancer to guide project success towards the
clinic (Aims 1-3).