Project Summary


Increased fat surrounding the prostate is linked to more aggressive disease


We currently understand remarkably little about how fat promotes prostate cancer


The fat surrounding the prostate releases chemical signals into the area around it


These signals are different in men with obesity compared to lighter men


Some of these signals may even tell the prostate cells to grow, leading to cancer


Claire and Charlotte will explore how these signals change cancer growth and spread


They aim to identify new drug targets and markers for aggressive disease


Ultimately, they hope to repurpose existing drugs to treat prostate cancer

About the Researchers

Imperial College London

Dr Claire Fletcher

Principal Investigator

Claire is an Imperial College/AstraZeneca Research Fellow within the Department of Surgery and Cancer at Imperial College London, where she completed her PhD and post-doctoral studies. Prior to this, she studied for a BSc in Cell Biology at Durham University and a MRes in Biomedical Research at Imperial College. Her research concerns the role of fat in promoting aggressive prostate cancer. She also investigates how non-coding RNAs, the so-called ‘dark matter’ of the genome, play a role in prostate cancer development and how they can be used to develop better treatments.

Professor Charlotte Bevan

Principal Investigator

Charlotte undertook her PhD at Cambridge University focussing on how androgens (the class of steroid hormones that includes testosterone) exert their effects and how this can go wrong in childhood development. It is this pathway that also drives prostate cancer, and her work since has been on understanding and therapeutically exploiting the androgen pathway in prostate cancer. This has expanded to include crosstalk with non-coding RNAs, and their use as biomarkers and therapy targets.

Obesity: a complex issue

Obesity is on the rise in the UK, and there are many reasons for this.


While it is important to eat healthily and be active, our weight is also affected by factors beyond our control, such as our genetics, our environment, how economically comfortable our lives are, our working conditions, and our childhood. Certain medical conditions and indeed, certain medications, including some used to treat prostate cancer, can also affect our weight.

We know that being overweight or obese may increase a person’s risk of developing aggressive prostate cancer, which means it will be more likely to spread and become life-threatening. We also know that obesity is driven by a complicated set of factors, and that we must make sure that effective treatment options exist for all prostate cancer patients, regardless of their weight.

Claire and Charlotte hope that their research will uncover features of aggressive prostate cancers, which could also act as potential targets for new treatments. In the long term, this could enable drugs developed for other diseases to be repurposed and used to treat prostate cancer.

The link between fat and prostate cancer

Studies have shown that increased fat surrounding the prostate is linked to more aggressive disease and poor treatment response.


However, we currently understand remarkably little about how fat promotes prostate cancer.

The fat surrounding the prostate releases chemical signals into the area around it. These signals are different in men with obesity compared to lighter men . Some of these signals are also known to change the behaviour of cells and may even tell the prostate cells to grow, leading to cancer.

Identifying features of aggressive disease will enable doctors to detect those patients who need early treatment and those who may be able to avoid treatment and side effects such as incontinence, erectile dysfunction, and body changes such as the growth of breast tissue. This will benefit those who are healthy weight, as well as those who are overweight or obese.

The research project


Claire and Charlotte will analyse fat from around the prostate and tumour samples taken from men who are undergoing prostatectomy. They will identify and compare the molecules in the samples from patients with and without obesity and explore how these molecules affect the behaviour of prostate cancer cells grown in the lab. Clinical data and information on diet and lifestyle will also be collected from these men. This will enable the researchers to find patterns between a person’s lifestyle and the aggressiveness of their prostate cancer in future studies. They hope to identify new drug targets and markers for aggressive disease.

 

Dr Claire Fletcher

Learning more about how fat promotes prostate cancer will strengthen the case for funding programmes to empower and support people to make lifestyle changes and improve their health. This would also decrease people’s risk of other diseases linked to obesity.

The future


This project is still in the early stages and Claire and Charlotte are still collecting samples and beginning to look at the signals released by the fat collected from patients. They hope to reveal how fat around the prostate promotes cancer and use this knowledge to identify features associated with aggressive disease and new ways to treat it.

Collaborations and partnerships


Claire and Charlotte will be working researchers from across the UK to deliver this research project, including scientists from Imperial College London, the University of Nottingham, the Institute of Cancer Research, and the University of Manchester. They will also be working with clinicians from Imperial College NHS Trust with expertise in treating prostate cancer.

“We are delighted to receive this Research Grant from PCR and have their support for our work. Our PCR-funded research will investigate how prostate tumours communicate with the fat that surrounds the prostate, and how this may fuels more aggressive types of prostate cancer often seen in overweight men. We hope that, by identifying the molecules responsible for obesity-driven prostate cancer, we can target these to develop new treatments for aggressive disease in general.”

Dr Claire Fletcher and Professor Charlotte Bevan
Imperial College London
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