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27 September 2012
Two research groups within the School of Biosciences have received research funding of over £450,000 to investigate the causes of, and new therapies for, breast cancer. Senior lecturers, Dr Matt Smalley of the European Cancer Stem Cell Research Institute and Dr Richard Clarkson of the School of Biosciences, have independently received awards from the Breast Cancer Campaign and Cancer Research Wales for their ongoing research.
Dr Smalley has been funded by Breast Cancer Campaign to investigate the role of a ‘molecular switch’ called Lyn kinase in both the normal breast and a highly aggressive breast cancer subtype called ‘triple negative’ disease.
"We think that high activity of Lyn kinase in cells in the normal breast creates the conditions for them to become triple negative tumours," says Dr Smalley. "The fact that high activity is maintained in the tumours, makes Lyn kinase a candidate for rationally designed targeted therapies, something that has not previously been available for this tumour type."
Dr Smalley’s project will address the mechanisms that Lyn kinase uses to regulate normal and cancerous breast cells and will also carry out initial tests to determine whether Lyn kinase holds promise as a future therapeutic target. Success in these studies has the potential to lead to new treatment options for patients with this aggressive breast cancer subtype.
Dr Clarkson has also been funded by Breast Cancer Campaign to extend his research group's studies on the potential of a new anti-cancer agent, TRAIL, for patients who have relapsed and become resistant to anti-hormonal therapy.
"Our preliminary laboratory studies suggest that breast tumour cells that have acquired resistance to tamoxifen are exquisitely sensitive to TRAIL" Dr Clarkson explained. "This research project brings together basic and clinical scientists from across the Cardiff area to determine whether this effect is observed directly in patient tumours."
Co-investigators Dr Julia Gee of the School of Pharmacy and Prof. Peter Barret-Lee , Consultant Clinical Oncologist at the Velindre Cancer Centre will help to co-ordinate the sampling and analysis of tumours outside the body, testing the efficacy of TRAIL as a second line therapy for patients with relapsed disease.
Dr Lisa Wilde, Director of Research, Breast Cancer Campaign said, "We’ve made great advances, but we can’t stop now if we want to beat breast cancer, the UK’s most common cancer with 48,000 new cases diagnosed each year. It is important that we make more effective treatments that target breast cancer in multiple ways, particularly for patients who have aggressive types of breast cancer, or whose tumours have become resistant to existing therapies. They currently have limited treatment options and that is why Campaign is proud to be funding this crucial work."
In a separate interconnected program of work on TRAIL-based therapy, and in collaboration with Dr Andrew Westwell and Dr Andrea Brancale of the School of Pharmacy, Cancer Research Wales has funded a PhD project within the Clarkson lab to look at the role of the gene c-Flip in causing resistance to the agent TRAIL. "Our published study performed by my PhD student, Luke Piggott who will be staying with the group once qualified to work on this research program, showed that suppressing c-Flip can sensitize breast cancer stem cells to TRAIL."
The new project will investigate how this happens and aims to develop a drug to inhibit c-Flip, which if successful could be used to improve efficacy of TRAIL in breast cancer patients.
Dr Lee Campbell at Cancer Research Wales comments, "We are proud to support an exciting project that seeks to directly target breast cancer stem cells. These infrequent, yet problematic cells are proposed to give rise to the treatment resistant cell population that leads to relapse. The targeting of c-FLIP within these cells provides a new approach to the treatment of difficult breast cancers. We very much look forward to the design and generation of inhibitors that can be taken forward for pre-clinical and clinical evaluation."
School of Biosciences
School of Pharmacy
European Cancer Stem Cell Research Institute
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