Award to explore genetic weaknesses of prostate cancer

Claire Fletcher (1)

Dr Claire Fletcher successfully secured the John Black Charitable Foundation-Prostate Cancer Foundation Challenge Award ($530,950) to investigate DNA damage and immune response in advanced metastatic prostate cancer.

Dr Fletcher is a postdoctoral career development fellow in the Department of Surgery at Imperial College London. Earlier this year she was awarded an Imperial College Research Fellowship, jointly funded by AstraZeneca and NIHR Imperial BRC, to continue her research into mechanisms of biogenesis regulation under the mentorship of Professors Charlotte Bevan and Robert Brown at Imperial College London, and Dr Molly Taylor at AstraZeneca.

MicroRNAs are small non-coding RNA molecules that regulate gene function post-transcriptionally. MicroRNAs are evolutionarily conserved and dysregulated in many human disease, implying indispensable biological functions. In this project, Dr Fletcher aims to systematically identify kinases that regulate production of microRNA, which could open opportunities for development of highly informative disease biomarkers, and patient-tailored treatment strategies across multiple diseases.

Dr Fletcher’s prior research has demonstrated that targeting of NORAD, a long non-coding RNA that maintains chromosomal stability and DNA damage repair (DDR) mechanisms, could sensitise prostate cancers to chemotherapy and immunotherapy. She has also revealed a novel role for NORAD in promoting degradation of a DNA-damaging microRNA. With the John Black Charitable Foundation-PCF Challenge Award, Dr Fletcher and colleagues will investigate NORAD and its targeting microRNAs as biomarkers for DDR deficiency and response to treatment, as well as novel therapeutic targets for advanced prostate cancer. The team will also investigate how NORAD modulates immune cell infiltration into prostate tumours, and how this may dictate immunotherapy response in prostate cancer patients. This multidisciplinary project will be led by Dr Fletcher and Prof Bevan, in collaboration with Prof Karen Knudsen (Thomas Jefferson University), Prof Johann de Bono (Institute of Cancer Research), and Prof Ian Mills (University of Oxford).

PCF Challenge Awards are given to teams of investigators who address significant problems in prostate cancer through multi-disciplinarity, novel research expertise and biotechniques. This reflects the ‘convergent science’ strategy of NIHR Imperial BRC Cancer Theme, aiming to bring together Imperial’s life and physical sciences, bioengineers and clinicians to tackle clinically-relevant questions in an innovative and multidisciplinary way.