Project No. 08

Hormone Therapy: Stopping resistance in its tracks

Investigating how prostate cancers become resistant to hormone therapy

S c r o l l   R i g h t

What could this achieve?

Hormone therapy is a mainstay of prostate cancer treatment but for many patients, it will eventually stop working. Dr Gaughan will investigate how this happens, identifying new targets for treatments to prevent resistance and ensuring that hormone therapy continues to be an effective treatment.

How?

Dr Gaughan and his team will use gene-editing techniques and two new methods they have developed to explore and identify the processes and key proteins behind resistance caused by AR-Vs.

The Future- what’s next?

The researchers will first identify the key proteins involved then conduct further testing to validate them as potential drug targets for future research.

What could this achieve?

Hormone therapy is a mainstay of prostate cancer treatment but for many patients, it will eventually stop working. Dr Gaughan will investigate how this happens, identifying new targets for treatments to prevent resistance and ensuring that hormone therapy continues to be an effective treatment.

How?

Dr Gaughan and his team will use gene-editing techniques and two new methods they have developed to explore and identify the processes and key proteins behind resistance caused by AR-Vs.

The Future- what’s next?

The researchers will first identify the key proteins involved then conduct further testing to validate them as potential drug targets for future research.

Project Start

January 2020

Research Facility

Newcastle University Centre for Cancer

Budget

£110,000/year

End

January 2024

We are delighted to announce that this project has been awarded The Martin Dallison Award, in honour of Martin Dallison’s contribution to prostate cancer research.

Hormone therapy

Hormones are chemicals that are used to send messages to different parts of the body. Male hormones like testosterone drive the growth and spread of prostate cancers by attaching to a protein called the androgen receptor. This ‘switches on’ the androgen receptor and it sends messages to the cancer cell to tell it to grow and divide. The androgen receptor has three different parts: the part that male hormones attach to, the part that tethers the receptor to DNA and the part that sends the message to switch on or off genes in the cancer cell.

Hormone therapy can stop male hormones switching on the androgen receptor. It sticks to the part of the androgen receptor that usually attaches to male hormones, meaning there is no room for the male hormones to attach.

The androgen receptor is switched on by hormones called androgens. When it is switched on, it sends messages to the prostate cancer cells telling them to grow and divide. Prostate cancers develop resistance to hormone therapy when shortened versions of the receptor called ARVs are formed.

The Problem with Hormone Therapy

Unfortunately, for many prostate cancer patients, hormone therapy will eventually stop working. One reason for this is the androgen receptor itself changes, so that the part that normally attaches to the hormone is missing. There’s nowhere for the hormone therapy to stick to, and so the receptor is always switched on. Therefore, messages telling the cancer cell to grow, and divide continue to be sent. These forms of the androgen receptor are known as androgen receptor variants or ARVs. ARVs are found in around 70-80% of advanced prostate cancer patients.

At the moment, we don’t know how ARVs are made. Therefore, we don’t know how we can stop this process and keep hormone therapy working for prostate cancer patients.

Prostate Cancer Research Centre funded researcher Dr Luke Gaughan talks about his work investigating how prostate cancers become resistant to hormone therapy.

WHAT WILL THIS MEAN FOR PROSTATE CANCER PATIENTS

Luke and his team are investigating how ARVs are made and how this process could be stopped to prevent hormone therapy resistance. This would lead to a new and better way to treat advanced prostate cancer that lasts longer than current therapies. Resistance to hormone therapy could be delayed, reversed, or even avoided completely.

Luke's Research Project

The researchers have developed cutting-edge technology in order to give them powerful insights into how ARVs are made in advanced prostate cancer cells. They will identify key proteins that are involved in ARV production and the growth and spread of prostate cancer. The researchers will then conduct further tests to establish whether these proteins have the potential to be drug targets. Once potential targets have been established, drugs could be developed that block these proteins, stopping the production of ARVs and preventing resistance to hormone therapy.

The Future

The researchers are currently identifying the proteins involved in ARV production. In the long term, they hope that their project will lead to the development of new drugs. These will then undergo clinical trials and eventually become a new treatment for prostate cancer.

Collaborations and Partnerships

Luke is working with two co-investigators from the Newcastle University Centre for Cancer, Professor Craig Robson and Mr Rakesh Heer. To bring their project to life, they will be collaborating with other researchers from the Centre for Cancer and the University of Athens.

“Together with my co-leads on the PCRC-funded project Mr Rakesh Heer, Consultant Urological Surgeon, and Prof Craig Robson, we will be undertaking a super novel approach to study how we can prevent advanced prostate cancer-associated forms of the androgen receptor being generated. By blocking this process we will be able to prevent disease progression. We are thrilled to be part of the national PCRC research team and are very much looking forward to helping deliver new targets for future treatments to help men with prostate cancer.”

Dr Luke Gaughan
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