Developing targeted drugs to treat advanced 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.

Why did we fund this project?

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.
• Building on work we previously funded to characterise how microRNAs affect prostate cancer growth, the team 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 have confirmed that in almost all men with prostate cancer there are many changes in the genetic code of normal prostate tissue.
• The team showed that ‘normal’ prostate cells in men who had prostate cancer had more mutations than ‘normal’ prostate cells from men without prostate cancer.
• Based on the genetics of the samples analysed, the team can create maps to understand where the different mutations occurred. The team showed that in most men the mutations in normal cells are different to mutations in cancer cells.
• We now know that large regions of the prostate in men with prostate cancer harbour a number of mutations, making it an ideal place for new cancers to grow. The whole prostate is primed and ready to develop prostate cancer driven by an, as yet unknown, biological process.

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.