Targeting prostate cancer cells’ antennae to treat advanced prostate cancer

Grant information

Researcher: Dr Adriana Buskin
Institution: Newcastle University
Grant award: £350,000
Reference: TLD-CAF23-007

What you need to know

• All our cells have an ‘antenna’ on their surface, picking up signals sent by their surrounding environment.
• Prostate cancer cells at early stages also have this antenna, which means they can grow when they detect hormones like testosterone – or stop growing when testosterone is blocked by hormone therapy.
• Prostate cancer cells that lose this antenna stop responding to hormone therapy, because they no longer sense important cues and fail to convert signals into cellular responses.
• Dr Buskin will look at why these cells lose their antennae, and if there is a way to restore them – and if this makes the cells respond to hormone therapy once more.

About Dr Adriana Buskin

After graduating in biological sciences, Dr Buskin completed her master’s degree in genetics and molecular biology, in Universidade Federal de Pernambuco, Brazil.

She then moved to the UK to work with cancer research, before starting a PhD at Newcastle University. Dr Buskin’s PhD looked at mutations in the same ‘antenna’ this project will focus on, but in the context of a degenerative eye disease. To do this, she used stem cells to grow 3D models of the disease to study its development.

Since finishing her PhD in 2020, Dr Buskin has been working with Professor Rakesh Heer, who is based at Imperial College London and Newcastle University. In that time, she has been applying her skills in growing 3D models of diseases from stem cells to better understand the biology of prostate cancer.

In 2021 Dr Buskin was funded by the NC3Rs to develop a pioneering 3D human prostate model from stem cells, for drug testing, free of animal tissue and animal-derived materials. She will use this model to study drug resistance in prostate cancer.

This fellowship will enable her to extend this promising research further as an independent researcher.

What will Dr Adriana Buskin do?

All our cells have a little ‘antenna’, known as the primary cilium, on the outside. This antenna can detect nearby chemical signals and relay these signals to the cell. This is one way that our bodies tell their cells what to do.

These signals include hormones, which are used by the body to regulate all kinds of processes, including puberty and pregnancy. But when prostate cancer cells detect hormones like testosterone, this encourages them to keep growing and spreading. That is why hormone therapy aims to stop your body making testosterone, or to stop the cancer cells from being able to access it.

Unfortunately, hormone therapy can eventually stop working, and the cancer starts growing again, even without testosterone.

Dr Buskin’s research focuses on why this happens. Previous research has shown that prostate cancer cells sometimes lose their antennae – and she believes that this can drive prostate cancer to become resistant to treatment.

In this project, Dr Buskin will explore exactly how prostate cancer cells lose their antennae. Knowing what is behind the loss, she will then look for a way to reverse the process and restore the antennae – and then test whether these cells start responding to hormone therapy again.

She will do this research using lab-grown ‘miniature tumours’, known as organoids. These organoids are 3D models of advanced prostate cancer, and give researchers a more accurate idea of how the disease responds in real life than cells grown flat in a dish – making it easier to move the research into mice and, later, men with prostate cancer if the results are promising.

For this project, Dr Buskin will work in collaboration with Professor Felix Feng at the University of California San Francisco, USA.

As well as regular virtual meetings with Professor Feng, Dr Buskin will spend a month in his lab, learning data processing techniques and accessing his lab’s library of cancer cells from men who have been treated with hormone therapy. This will enable her to narrow down the list of potential ways to restore the cells’ antennae.

How will this benefit men?

When prostate cancer becomes resistant to current treatments, it leaves men with limited options.

Dr Buskin’s research into exactly how and why prostate cancer stops responding to hormone therapy could lead to trials of new treatments that can stop or reverse this process.

This would enable men who have stopped responding to treatment to benefit from hormone therapy once again, extending their lives. It could also lead to new treatments that are less likely to lead to resistance, benefiting men at the earlier stages of prostate cancer too.