Hormone Therapy: Stopping resistance in its tracks

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.

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.

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.