Identifying the early changes that drive treatment resistance

Grant information

Researcher – Dr Juan Manuel Jiménez Vacas
Institution – Institute of Cancer Research
Award - £268,435
Duration - 2021-2024
Reference – TLD-PF19-006

Why did we fund this project?

• Many effective treatments for advanced prostate cancer, such as enzalutamide and abiraterone, work by blocking the growth signals that prostate cancers need to grow and spread.
• Eventually, prostate cancers adapt to be able to grow and spread even when these growth signals are blocked. When this happens, these treatments stop working and the cancer becomes resistant.
• Dr Juan Manuel Jimenez Vacas and team want to understand the changes in prostate cancer cells that lead to cancer becoming resistant.
• The team are particularly interested in changes that occur immediately after men start treatment.
• Uncovering these ‘early’ changes could identify targets for drugs that could be given in combination with the current treatments to keep them working for longer.

What did the team do?

• The team studied prostate tissue removed from men as part of their usual surgery, to identify early changes after treatment.
• They further examined these changes in prostate cancer cells grown in the lab.

• The team also used a special mouse model where prostate cancer tissue from men is implanted. This allows the prostate cancer tissue to be studied in a more realistic environment.
• This fellowship also supported Juan to travel to Harvard, to work with another leading prostate cancer research team led by Professor Steve Balk. Here, he was able to learn new techniques and gain experience in a different research environment.

What did the team achieve?

• The team identified early changes in prostate cancer cells key to the development of resistance to treatments.
• Importantly, the team found that reversing these changes could reduce prostate cancer cells’ ability to survive and make them sensitive to treatments again.
• This suggests that reversing these changes could be a promising new way to help men benefit from treatments for longer.

What does this mean for men?

• The team’s work could lead to the development of treatment combinations that could work for longer than current treatments alone. The team now need to study these changes in more detail, to identify how best to target them with new combinations.
• These new treatment strategies could help extend how long treatment can keep prostate cancer under control, helping men live better for longer.