Enabling More Targeted Treatment of Prostate Cancer by De-coding Stress Response Signalling of Cancer Cells

Prof Ian Mills is a molecular biologist with a background in transcriptional regulation and membrane trafficking, based at the Nuffield Department of Surgical Sciences at the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust). He is the John Black Associate Professor of Prostate Cancer and also holds a secondary appointment as Professor of Translational Prostate Cancer Biology at the Centre for Cancer Research and Cell Biology at Queen’s University of Belfast. Ian studied Biochemistry as an undergraduate in Oxford, undertook his PhD training at the University of Liverpool, completed a postdoc at the MRC Laboratory of Molecular Biology in Cambridge, and has been running pre-clinical prostate cancer research groups since 2003.

Due to the high-incidence of prostate cancer relative to the proportion for whom the disease progresses, there is a risk of overtreatment.  By understanding prostate cancer biology Ian and his fellow researchers are aiming to discover molecular signals that will more reliably identify individuals with high-risk of developing lethal disease at the time of diagnosis.  This will enable treatment to be targeted more effectively and reduce treatment of patients without lethal disease, and the associated side effects. In addition disease progression can take a number of years post-diagnosis and there is therefore a time window in which treatments targeting particular molecular properties of the disease can be used to slow or stop progression, if the relevant driving biology is known.  Historically the research in this field is focussed on androgen receptor signalling, but other biological drivers are now known to contribute too.

Ian is studying how metabolic changes in prostate cancer modify the cancer genome, the tumour micro-environment and the stress response signalling of cancer cells to support treatment resistance and disease progression.  He is also working on how inherited/germline genetics impacts on this evolution and developing risk scores with collaborators based on these factors.

The hope is that Ian’s research will help to select patients for early cancer screening and lead to the repurposing of clinically approved metabolic drugs for the treatment of prostate cancer.  If successful, this could ultimately reduce prostate cancer mortality although that would be in the long term.

Within Oxford Ian collaborates with the Nuffield Department of Surgical Sciences (Dr. Alastair Lamb, Prof. Freddie Hamdy, Prof. Richard Bryant), the Target Discovery Unit (within the Nuffield Department of Medicine) (Prof. Jens Rittscher), the Big Data Institute (Dr. David Wedge), and the Nuffield Department of Population Health (Dr. Ruth Travis).

Further collaborators within the UK are Dr. Charlie Massie (University of Cambridge), Prof. Andy Lynch (University of St Andrews), Prof. Ros Eeles (The Institute of Cancer Research), Dr. Zsofia Kote-Jarai (The Institute of Cancer Research), Dr. Simon McDade (Queen’s University Belfast), Dr. Karl Butterworth (Queen’s University Belfast), Dr. Eileen Parkes (Queen’s University Belfast), Dr. Emma Evergren (Queen’s University Belfast), Prof. Richard Martin (University of Bristol), Prof. Silke Gillessen (University of Manchester).

Internationally, Ian collaborates with Dr. Alfonso Urbanucci (Oslo University Hospital), Dr. Harri Itkonen (University of Oslo), Prof. Lisa Butler (University of Adelaide), Prof. Paul Rennie (University of British Columbia), Prof. Massimo Loda (Dana Farber / Harvard Cancer Centre).

Ian’s work is funded by the John Black Charitable Research Foundation, the John Fell Fund, UCARE, the Norwegian Research Council, and the Medical Research Council.