Both obesity and prostate cancer are major health problems in the UK, affecting 1 in 3 and 1 in 8 men respectively. Moreover, obesity increases the risk of developing aggressive disease and the risk of prostate cancer spreading. How this happens is not known. We want to understand how fat cells communicate with prostate cancer cells. A likely route is via exosomes, which are small bubbles released by cells that can carry genetic information and proteins. Our scientific aims are as follows:

  1. Grow prostate cancer and adipose tissue explants
  2. Isolate exosomes, then investigate how fat and cancer exosomes affect known cancer processes
  3. Prove that exosomes are transferred between fat cells and cancer cells, the investigate how fat cells affect gene regulation in cancer cells
  4. Identify what transferred exosomes contain and how do they differ between lean and obese patients

Once we have discovered how being lean or obese affects prostate cancer progression, we will look at treating patient samples and cells to see how existing prostate cancer drugs differ in their effect on the progression of cancer in obese vs lean men. Results from this study will show whether any underlying changes are drug targetable and which drugs are most likely to succeed. The information generated will contribute to our understanding of why obesity and cancer seem to be linked and provide a detailed understanding of prostate cancer risk factors at a molecular level. We intend on collecting a large array of medical and non-medical data through symptom and quality of life questionnaires, lifestyle and environmental questionnaires as well as reviewing magnetic resonance imaging (MRI), medical notes, drug and personal history, and previous blood tests. This is to ensure that what we observe in the laboratory is definitely caused by differences in lean and obese men, and not due to other causes of prostate cancer risk such as ethnicity, presence of urinary tract infections or drugs, which may alter the genes in tissues and therefore our results. As part of our initiative to digitize NHS information for easier analysis and dissemination of results, I have proposed the use of an Electronic Sample Tracking Database (ETSD) for this study, which is also available on iOS and Android. This will allow patients to complete their study questionnaires in comfort at home on their phone, iPad, PC or Mac, or on the ward post-operatively on an iPad. Paper questionnaires will also be available. However, consent forms will continue to be on paper. An overview of the identification and transport of patient samples is below:

  1. Patient is referred by GP
  2. Patient undergoes MRI scanning
  3. MRI results are reported by a radiologist
  4. Patient is discussed at multidisciplinary team (MDT) meeting and radical prostatectomy offered
  5. A research fellow identifies the patient from MDT as appropriate for study
  6. Patient is invited to outpatients and consented for surgery and study, patients are given a unique sample ID and assigned to the ETSD
  7. Once consented, patient is offered the questionnaires to complete either pre or post-operatively electronically or on paper
  8. Patient undergoes radical prostatectomy
  9. Samples collected intraoperatively and directly deposited under strict specified conditions and temperature into a sealed container
  10. Samples transported by courier service from Charing Cross Hospital operating theatres to Hammersmith Hospital where a scientist will process the samples

To ensure our consent forms and information leaflets are understandable to patients, we asked two patients and their family members to review the consent forms and information leaflets. We have also recruited two permanent members of the public recommended by Prostate Cancer UK as lay members to join our annual/biannual committee to discuss the progress and dissemination of this study. We plan on presenting results through our website, journals or news media.

Clinical trials registration: https://clinicaltrials.gov/ct2/show/NCT04167722?term=exopro&draw=2&rank=1

  

Study references and licenses: IRAS 262452, JRCO 19HH5065, NHS REC 19/LO/0754
ClinicalTrials.gov Identifier: NCT04167722 
Pathology reference number: QN862