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Research points to new therapies for bladder cancer

Posted on 9 July 2014

A University of York scientist has played a key role in research that could help to improve the treatment of muscle-invasive bladder cancer, one of the most common cancers, particularly among men.

Bladder epithelial cells grown in the lab are scratched to create a wound, which is self-repaired. This "regenerative" process involves a growth factor called amphiregulin, which triggers the Epidermal Growth Factor Receptor pathway in the same cells. The new research shows this pathway is hijacked by a subset of very aggressive bladder cancers, opening the possibility of using therapeutic inhibitors against the EGFR pathway to block these tumours.

Professor Jenny Southgate, Director of the Jack Birch Unit for Molecular Carcinogenesis, in the Department of Biology at York, is part of an international team that has discovered a particular aggressive form of muscle-invasive cancer. This form of tumour could potentially be treated using drugs that target the epidermal growth factor receptor (EGFR) signalling pathway which controls cell proliferation.

The research, led by Dr François Radvanyi of the Institut Curie and CNRS (Le Centre national de la recherche scientifique) in France, also identified specific biomarkers of this tumour sub-type and showed that potential targeted treatment was effective in preclinical models. The multi-disciplinary research, which involved biologists, bioinformaticians, statisticians, pathologists and clinicians, is published in Science Translational Medicine.

The number of new cases of bladder cancers diagnosed in the UK was 10,399 in 2011, with up to 30 per cent of patients developing invasive tumours which infiltrate the muscle of the bladder. The standard treatment of this form of cancer is the surgical removal of the bladder, though only around half of the patients have a life expectancy of more than five years after this procedure. Up to now, no targeted therapy has proven to be effective in these tumours.

Analysis of gene expression of 383 invasive bladder tumours enabled the researchers to identify a particularly aggressive group of tumours, representing around 24 per cent of bladder invasive tumour cases. The researchers analysed the molecular changes in this group, which revealed a permanent activation of the EGFR signaling pathway which controls cell proliferation. This signaling pathway, therefore, constitutes a promising therapeutic target.

The genetic expression profile of the tumours was found to be very similar to a particular type of basal-like aggressive breast cancer tumours. The identification of a preclinical model of basal-like bladder cancers enabled the researchers to test the efficacy of an anti-EGFR drug, which resulted in a significant reduction in tumour progression. The researchers have also found biomarkers allowing the identification of patients who might benefit from this treatment.

Professor Southgate said: “This research represents a true hope for treatment of this aggressive group of bladder invasive cancers for which there are very limited therapeutic options.  We work closely with the French group and our research in York was important in highlighting the EGFR pathway in this tumour group."

The research was funded by La Ligue Contre le Cancer under its “Tumour identity cards” (CIT) programme.  Professor Southgate is funded by York Against Cancer who part supports the research programme of the Jack Birch Unit for Molecular Carcinogenesis in the Department of Biology, University of York.

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