Hidden hormones: What drives prostate cancer after treatment

Prostate cancer is the second most commonly diagnosed cancer in men globally. When it comes to prostate cancer, steroids are everything. Steroids are not just what athletes use to enhance their performance.

Steroid hormones are made in our bodies to regulate a lot of processes such as blood pressure, acne and metabolism. We have long known that testosterone helps prostate cancer grow - which is why hormone therapy called androgen deprivation therapy (ADT) has been the first line treatment for advanced cases. But here is the problem: Ever wonder why sometimes, even after testosterone is gone, the cancer keeps growing?

That is the question I have been chasing in my research and what I found surprised me completely.

Everyone expected testosterone to disappear after treatment, as testes are shut down completely so no production of these potent sex hormones. But hiding in plain sight was another powerful hormone: 11-ketotestosterone (11-KT). When I analysed the levels of this hormone in blood samples from men on ADT, there it was. 11-KT, was not only still present but was actually the most abundant hormone left in the body.

My first question was: Could this "understudied" hormone which can only be measured now by advanced technology really be overtaking potent hormones after treatment? The answer was YES. And even more surprising? It can do what testosterone does: activate the receptor and help cancer grow.

This quiet, unnoticed hormone might be a key reason why prostate cancer keeps fighting back, even when we think we have shut off its fuel supply. So, the key is if we can test for 11-KT levels, we might be able to predict who is at risk and find better ways to treat them.

But there is more to this resistance than just the sex hormones, and that is the individual's genetic makeup. I have found that patients can respond differently to ADT based on their genetic makeup. A certain variant of an important gene makes it easier for the body to turn hormones from adrenal sources into 11-KT and fuel the growth of cancer cells. So, men with this gene variant tend to have higher levels of these hormones even after treatment. This means they might not respond as well to treatment. But if we test for this gene early, we could choose targeted treatments that work better for these patients.

My research shows that understanding both hormones like 11-KT and genetic differences can help us give more personalized care to men with advanced prostate cancer. Not every patient is the same and so their treatment should not be either.

Sadia Akram
The writer is a doctoral researcher in Turku Bioscience Centre. Her research is based on how hormones and genetics affect prostate cancer, especially at advanced stages. The goal of the research is to help doctors predict the treatment response in patients and to find better ways to treat each patient based on their unique biology.