Tissue study turns tables on prostate cancer

As we heard yesterday , a man’s lifetime risk of developing cancer is set to climb to one in two by 2027, and one of the biggest reasons is an increase in prostate cancer rates.

But research is bringing hope that more and more men will survive this disease and, based on recent progress, we have every reason to be optimistic.

Over the past couple of years we’ve made significant strides in prostate cancer research and treatment. This year the drug abiraterone (Zytiga), which our researchers helped to develop, was approved across the UK for men with advanced prostate cancer. And other important new drugs have emerged recently from research around the world and are showing promise in clinical trials, including enzalutamide (Xtandi), cabazitaxel (Jevtana) and radium-223 (Alpharadin).

Our researchers labs around the UK are also making progress in prostate cancer (such as in drug development, targeting cancer’s energy supply, finding gene faults that drive the disease and control how fast it grows and developing new types of therapy) and in the clinic (for example in hormone therapy, radiotherapy and more personalised treatment) as well as improving screening. And through our role in the International Genome Consortium prostate cancer project, we’re using the latest technology to understand prostate cancer’s genetic secrets and drive forward future advances.

It’s clear that momentum is gathering and things are moving faster than ever before. And now an important new study from scientists at our Cambridge Research Institute, published in the journal Cancer Cell, reveals a completely new gene network that can carry on driving advanced prostate cancer after patients become resistant to hormone treatment.

The findings paint a new picture of the processes that drive prostate cancer, and shed light on how we might be able to tackle it more effectively in the future. To find out more, watch this brilliant little video featuring lead researcher Naomi Sharma and some Lego:

[youtube=http://www.youtube.com/watch?v=JWA1LyTNq78]

Let’s look in a bit more detail at what the Cambridge team did, and how their discovery could help us beat prostate cancer sooner.

Tissue studies to tackle treatment-resistant tumours

A lot of the work on the molecular ‘nuts and bolts’ of prostate cancer has used cancer cells grown in the lab. Known as cell lines, these were originally taken from tumours many years ago and, as long as they’re kept warm and fed with nutrients and oxygen, they’ll grow happily in plastic Petri dishes indefinitely.

Although cell lines have proved to be very useful in helping researchers to understand some of the processes that drive cancer, or for testing new treatments, they’re not perfect. They tend to pick up genetic quirks that make them less like the original tumours they came from, and therefore less like the disease in an actual patient.

To get a better picture of what’s going on in real tumours, Dr Naomi Sharma and her team looked at fresh prostate tumour samples from men with the disease, searching the tumours’ DNA for ‘docking sites’ for a protein called the androgen receptor – these docking sites are molecular ‘switches’ that activate genes when the androgen receptor sticks to them.

Usually, the androgen receptor can only switch on genes – and drive prostate cancer – in the presence of male hormones like testosterone. Many men with prostate cancer are treated with hormone therapy that stops hormones driving androgen receptor activity in their cancer, halting its growth for a time.

But all too often, the treatment stops working – genes somehow get switched on even in the absence of hormones, and the cancer starts growing again.

Studying the switches – a world first

Previously, research using cell lines had suggested that the androgen receptor wasn’t so important in driving advanced prostate cancers that have become resistant to hormone therapy. But in recent years, scientists have found that experimental drugs that interfere with androgen receptor activity can indeed influence advanced cancers, showing that things are a bit more complicated than the lab experiments suggest.

To solve the puzzle, Dr Sharma and her team carried out the world’s first comprehensive study of prostate cancer tissue, comparing androgen receptor docking sites in the DNA of samples from ten men with prostate cancer, with five of them no longer responding to hormone therapy, two responding to treatment and three still untreated. They also took samples from two men with a condition called benign prostate hyperplasia, where abnormal cells grow in the prostate but aren’t cancerous.

The scientists discovered that the androgen receptor was docked on to a completely different set of genes in fresh prostate tumour samples compared with prostate cancer cell lines. There were also key differences between samples from men with early stage cancer and those with advanced cancer that had spread and become resistant to treatment. In particular, they found that genes involved in energy production were switched on in advanced cancers, providing fuel for tumours to grow.

Where next?

These results are eye-opening for prostate cancer researchers around the world. For a start, they highlight crucial differences between cancer cells in Petri dishes and those in patients. The scientists also looked at mice that had been transplanted with human prostate cancer cells and found that the patterns of androgen receptor docking and gene activity in their tumours more closely resembled those of fresh prostate cancer samples. So while cells grown in the lab may be useful for some experiments, they’re not an entirely accurate reflection of what’s going on in people or animals.

There are also big implications for future treatment and monitoring of prostate cancer. Dr Sharma and her team have figured out a ‘signature’ of 16 genes that can predict whether a man’s tumour is likely to be resistant to hormone therapy or come back after treatment. This could lead to the development of prostate cancer biomarkers – molecular ‘flags’ that allow doctors to monitor how well a patient’s disease is responding to therapy.

And finally, the research throws up a number of interesting leads for future prostate cancer treatments, particularly drugs targeting energy production in cancer cells – a hot topic in research at the moment– which can now be taken forward by researchers around the world.

More than 10,000 men die of prostate cancer every year in the UK, and we urgently need more effective approaches for fighting this disease. By funding this research, and more like it, we’re working towards a day when all prostate cancers are cured.

Kat