Evaluating Chemosensitivity of Bladder Cancer Cell Models with Inactivating Mutations in ZFP36L1 Found in a Significant Proportion of Bladder Cancer Patients

There is a need to develop new targeted therapies for bladder cancer.  Recent insights from analysis of bladder cancer genetics have identified some potential new therapeutic targets or 'vulnerabilities'.  In this project, we are focussing on evaluating one such potential novel vulnerability found in more than 8% of bladder cancers.  We will systematically test whether bladder cancers with this vulnerability are more easily killed by existing cancer drugs.  This results from this study could open the way for development of new targeted therapies for treatment of a significant bladder cancer patient subgroup that display this vulnerability.

Background: Over 8% of human bladder cancers have been shown to possess ZFP36L1 inactivating mutations (TCGA bladder cancer dataset).

Recent genetic analysis of bladder cancer has uncovered some previously unrecognised frequently mutated genes including ZFP36L1, a potential tumour suppressor gene. ZFP36L1 encodes an RNA binding protein that binds to adenine uridine (AU)-rich elements in the 3'UTR of mRNAs and mediates their degradation. It has recently been implicated as a driver gene in different cancers, including breast cancer.

The aim of the proposed project is to test how inactivating ZFP36L1 mutations in bladder cancer affects cell growth, clonogenicity, replication stress and susceptibility to chemotherapy.

Patient benefit: The results of the proposed project could have important implications for new treatment options for bladder cancer where few new treatments have been developed in the last thirty years. 

Project Lead:

Dr John Murphy, Genome Engineering Laboratory, School of Life Sciences, University of Westminster.    

 

Read about the other 2024 IOPP grant-awarded projects.