Impact of androgen deprivation therapy on microenvironment of PCa
Research type
Research Study
Full title
Study to explore the impact of androgen deprivation therapy on the tumour microenvironment in high risk prostate cancer
IRAS ID
211571
Contact name
Ananya Choudhury
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
The main purpose of this study is to explore the impact of hormone therapy in patients with high risk prostate cancer. The researchers will be collecting tissue samples at the point of diagnosis and after completing hormone therapy prior to high dose rate (HDR) brachytherapy. An optional blood sample will also be taken. This project is important to the public because it will improve our understanding of the impact of hormone therapy in patients with prostate cancer. Patients enrolled in this study will have standard treatment with combination HDR with EBRT as per routine clinical practice.
Lay Summary of Results
The progression of prostate cancer that doesn't respond to hormonal deprivation treatment (so called castration-resistant) is a big problem in medicine that hasn't been solved yet. We recently found a group of normal prostate cells that are resistant to treatment and have a specific marker called LY6D. We discovered that when a certain gene called PTEN is deleted in the prostate cells of mice, it leads to more LY6D+ cells. By studying these LY6D+ cells, we found that they have a way to help themselves grow and survive better by releasing a substance called amphiregulin, which activates a signaling pathway called MAPK. This makes the cells stronger and better at forming organoids. When we stopped this pathway with drugs, the LY6D+ cells became sensitive to treatment again, and they couldn't form organoids as well. Interestingly, we found that these LY6D+ cells are more common in aggressive and treatment-resistant prostate cancer (samples collected from the AToM study), which shows their importance in advanced stages of the disease. Our findings suggest that stopping the MAPK pathway early with drugs could help prevent castration-resistant prostate cancer from getting worse.
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: Study is not on a registry
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
If yes, describe or provide URLs to disseminated materials: Publication:
Steiner I, Flores-Tellez T, Mevel R, Ali A, Wang P, Schofield P, Behan C, Forsythe N, Ashton G, Taylor C, Mills IG, Oliveira P, McDade SS, Zaiss DM, Choudhury AC, Lacaud G and Baena E.
Autocrine activation of MAPK signaling mediates intrinsic tolerance to androgen deprivation in LY6D prostate cancer cells.
Cell Rep. (2023) 42, 112377. 10.1016/j.celrep.2023.112377.https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F37060563%252F%2FNBTI%2FVKm1AQ%2FAQ%2Fb04db349-a1a7-4eb6-b357-76389d53d3c5%2F2%2FYnSSDyiS2Q&data=05%7C02%7Cstanmore.rec%40hra.nhs.uk%7C4a07c5bf2475412fa31d08dc80978f2d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638526635633595287%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=IEE01IEeiWIsuoMMbwE%2B8kDw5N4zmKG2UO%2Bs17%2BlKGI%3D&reserved=0
If pending, date when dissemination is expected:
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: No
If yes, describe and/or provide URLs to materials shared and how they were shared:
If pending, date when feedback is expected:
If no, explain why they haven't: Per initial IRAS, participants will not be informed of the results as the research study has no impact on participants clinical outcome
Have you enabled sharing of study data with others?: Yes
If yes, describe or provide URLs to how it has been shared: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F37060563%252F%2FNBTI%2FVKm1AQ%2FAQ%2Fb04db349-a1a7-4eb6-b357-76389d53d3c5%2F2%2FYnSSDyiS2Q&data=05%7C02%7Cstanmore.rec%40hra.nhs.uk%7C4a07c5bf2475412fa31d08dc80978f2d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638526635633601370%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=zzrLIf2p8JLDie6lqM8%2BOlulepTG%2B%2F3DuzXViw9DNBk%3D&reserved=0
If no, explain why sharing hasn't been enabled:
Have you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: Samples were returned to current holder of the samples - NHS pathology departments at the end of the researchREC name
London - Stanmore Research Ethics Committee
REC reference
17/LO/0379
Date of REC Opinion
3 Apr 2017
REC opinion
Further Information Favourable Opinion