Micro-control of the androgen receptor: a new approach to treating prostate cancer?

Grant information

Institution – Imperial College London
Researchers – Professor Charlotte Bevan & Dr. Claire Fletcher
Grant award - £588,628
Duration of funding – 2018-2023
Status - Complete
Reference – RIA17-ST2-017

Why did we fund this project?

• Androgen hormones are essential for the growth and function of the prostate, and the androgen receptor (AR) plays an important role in prostate cancer development.
• Hormone therapies that block androgen signals can be effective in treating prostate cancer, but the cancer can become resistant, causing the treatments to stop working.
• Professor Bevan and her team aimed to study newly discovered shorter forms of the AR gene which have been linked to prostate cancer that has become resistant to treatment.
• They wanted to investigate how these AR gene variants are controlled by tiny pieces of genetic material called microRNAs.

Watch the Spotlight on webinar for more information of the role of the AR in prostate cancer.

What did the team do?

• The team developed new computer-based methods to detect changes in the length of the AR gene.  They then looked at the length of the AR and other cancer-related genes in prostate cancer models. 
• The team also identified which microRNAs could bind to both the full-length AR and the shorter AR variants.
• They then tested how changing the levels of these microRNAs in cancer cells affected androgen signalling and cancer cell growth.

What did the team achieve?

• The team discovered that changes in the length of the AR gene and other cancer-related genes are linked to faster progression of prostate cancer, and that different variants of the AR gene are present in cancers that are resistant to hormone therapy.
• They identified two particularly interesting microRNAs that can bind to both the full-length AR and the shorter AR variants.  These microRNAs can influence the growth of prostate cancer cells, and their effect depends on which versions of the AR are present.
• They also found that the levels of these two microRNAs are altered in hormone therapy-resistant cancer cells, and their abundance can affect how quickly prostate cancer progresses.

What does this mean for men?

• The discovery of microRNAs that can affect the androgen receptor and influence cancer cell growth could pave the way for new approaches to treating prostate cancer.
• The team will continue to investigate the potential of the two identified microRNAs as promising targets for drug development.
• This research could lead to new treatments for men whose prostate cancer has stopped responding to hormone therapy.