22 Jan 2014

Fighting back against hormone resistance in prostate cancer cells

Prostate Cancer UK scientists show that vitamin D receptor activation can lead to testosterone breakdown in prostate cancer cells.

Prostate Cancer UK scientists show that vitamin D receptor activation can lead to testosterone breakdown in prostate cancer cells.

Once prostate cancer becomes resistant to hormone therapy, there are few treatment options left, which is why a lot of research goes into finding out how cancer cells become resistant to hormone therapy, and whether there’s a way to prevent this.

How hormone therapies work

Most hormone therapies work by stopping the body from making testosterone.  This is a male hormone that binds to and ‘turns on’ another protein called the androgen receptor (AR), which in turn drives prostate cancer growth. So the idea is that by either stopping the body from producing testosterone, or by blocking its interaction with the androgen receptor, the AR will stay in the ‘off’ position, and the cancer won’t grow. And this does work for a while. 

But unfortunately, cancer is very good at getting around the body’s defenses. For example, after a while, cancer cells start to make their own form of testosterone-like hormone, that can turn on the androgen receptor and promote cancer growth – a process that is unaffected by the hormone therapy.

Can we beat cancer at its own game?

Dr Paul Thompson and his team of scientists at the University of Ulster have just published some promising new results, which might identify a way to tackle this problem. 

They have used prostate cancer cells to show that some vitamin D is made in the prostate, and that it works together with another protein, which is also found in the prostate, called the vitamin D receptor (VDR). The scientists showed that when the VDR is activated by vitamin D, or a man-made version of it, it turns on genes that are responsible for reducing the level of hormones, such as testosterone.

This research suggests that activating the vitamin D receptor can reduce hormone levels regardless of whether the hormone is made normally in the body or by cancer cells trying to overcome the effects of hormone therapy. So the scientists think that designing therapies that work by activating the vitamin D receptor, and using them together with traditional hormone therapies, could cancel out the problem of tumour cells producing their own testosterone. This would mean increased effectiveness of hormone therapy.  

Following up on a promising lead

These results are very promising, but obviously still need to be tested further in more complicated pre-clinical and clinical models. In addition, we can’t yet tell whether activating the vitamin D receptor will really be able to delay cancer cells becoming resistant to hormone therapy, because unfortunately, producing their own testosterone isn’t the cancer cells’ only escape route.  Prostate cancer can also become resistant to hormone therapy when the androgen receptor changes so that it can drive cancer growth without needing any hormones at all, and it’s not yet clear whether this would be affected by activating the vitamin D receptor.

The scientists are now moving on to test this idea in pre-clinical models, which will hopefully give a fuller picture of the potential of this research.

Dr Kate Holmes, Head of Research at Prostate Cancer UK, says, ‘it’s too early to say when, or if this research will progress from the lab and into the clinic, but it’s a promising avenue of research that could one day contribute to effective management of advanced prostate cancer.’