Project Summary


Hormone therapy is the main form of prostate cancer treatment


Hormone therapy will stop working for nearly all patients


Hormone therapy stops the androgen receptor (AR) from telling cancer cells to grow


The outside of the AR acts as a switch. When the switch is on, the AR tells cancer to grow


The switch is turned on by male hormones and turned off by hormone therapy


This project will explore how AR variants (ARVs) are made and how to stop this process


ARVs don’t have a switch so they are always on. Hormone therapy doesn’t work on ARVs


Preventing ARV production could keep hormone therapy working for longer

About the Researchers

Centre for Cancer, Newcastle University

Dr Luke Gaughan

Principal Investigator

Dr Luke Gaughan is a senior lecturer at Newcastle University. He has worked on several exciting projects studying the mechanisms of androgen receptor regulation in prostate cancer.

Dr Dominic Jones

Research Associate

Dominic is a research associate at Newcastle University. He will be using cutting edge technology to identify the key proteins involved in the production of androgen receptor variants and the growth and spread of prostate cancer.

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 (AR) 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.

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 cancers develop resistance to hormone therapy when shortened versions of the receptor called ARVs are formed.

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

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 and Dominic'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 PCR-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 PCR 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
Newcastle University
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