‘Meet the Scientists’: an opportunity to chat with the world-class researchers working on advanced prostate cancer

Science and Industry Museum, Manchester
9 March 2022

Dafydd Charles, OPCSG

Prostate Cancer Research (PCR) funds a wide range of projects whose aim is threefold – to reduce the symptoms of prostate cancer following diagnosis, to increase survival (and equally important, the possibility of a cure) and to improve the quality of life for people with prostate cancer. As its publicity literature states starkly, the research work being financially supported isn’t just about adding years to life, it’s also about adding life to years.

Meet the Scientists was a unique event at which scientists came together with families affected by prostate cancer in a relaxed, informal environment. It was a chance to come face-to-face with the people carrying out cutting edge research and hear directly from the horse’s mouth as it were, about what they are doing and how their fascinating and inspiring work will help people affected by prostate cancer. There were no lectures or formal presentations: scientists moved from table to table, having conversations about their work, and those invited had the opportunity to ask them any questions they liked, or simply to listen to the conversation around.

Twenty or more tables had been set out in a large room and the support group members (plus other half where they were present) allocated to each. It reminded me a bit like a wedding reception! – Sadly David James, the Head of Patient Projects and who spoke to the OPCSG in January, couldn’t attend as he had just tested positive for Covid. Following an introductory talk by the head of research and communications at PCR (Naomi Elster), the series of conversations kicked off. In each case the scientists introduced themselves and then an informal conversation took place, often in depth and often very personal in nature. It was electrifying and I got the impression that the scientists got as much out of this arrangement as did us patients and former patients.

Over the day, time constraints meant that each group was only able talk to six research teams in this way, though people were free during the breaks and buffet lunch to approach any of the much larger number attending. That said, I found the topics discussed at my table very inspiring indeed even though my own (relatively advanced) cancer appears to have been treated successfully using the ‘standard’ methods widely used in the NHS today.

The project teams that spoke at the table I was sitting at were as follows:

Blocking prostate cancer signals – the Wnt pathway

This project explores how a better understanding of how one way that cells communicate with each other (called the Wnt pathway) can be used to treat prostate cancer and offer new treatments to those men who have no other options. The researchers are particularly interested in how cancer cells spread to, and then continue to grow in bone, and also why some men have much greater numbers of bone metastases than others. This is one of the big unanswered questions in developing effective treatments for advanced disease.

Hormone Therapy: Stopping resistance to treatment in its tracks

We are probably all aware that the male hormone testosterone drives the growth and spread of prostate cancers. This is because it attaches to a protein on the surface of a cancer cell called an androgen receptor. This is the basis of how hormone therapy works – essentially it prevents testosterone from ‘switching on’ this receptor. In time however, hormone therapy loses its effectiveness, something that is caused by the receptor on the cancer cells itself changing (mutating). This very important research is investigating how these changed receptors are ‘made’ and how the process could be stopped to prevent hormone therapy resistance from developing. In this way resistance to hormone therapy could be delayed, reversed or even avoided completely.

ProCASP: could damaging DNA cure my cancer?

This project is investigating why damaging the DNA inside cancer cells only works as a treatment for some patients. DNA writes the code which makes our cells, but it is also fundamental to cancer as it is to life. DNA damaging agents (DDAs) can therefore be used to treat prostate cancer, examples include radiotherapy and most forms of chemotherapy as well as newer therapies like PARP inhibitors. DDAs work by damaging DNA, leading to the death of cancer cells. Unfortunately, DDAs do not work for everyone and at the moment and it is not clear why some patients benefit from these treatments while others do not. This can make it difficult to know the best way to treat an individual’s prostate cancer. Different cancers have unique features which make them suitable or unsuitable for a certain type of treatment. This project is investigating patterns in the DNA of tumours that can be used to predict which treatment will work best for the individual patient – an idea known as personalised medicine.

PTEN – finding the off-switch

There are two types of gene that are important in cancer: oncogenes which are like ‘on switches’ and tumour suppressor genes which are like ‘off switches’. The oncogenes tell cells to grow and make more copies of themselves. The tumour suppressor genes tell cells to stop growing and dividing, preventing cancer in healthy cells. These switches trigger chain reactions and exist as part of a complicated network, like the switches in a fuse box. When a normal cell turns into a cancer cell, it can sometimes be hard to work out which switch has tripped. PTEN is a genetic ‘off-switch’ which doesn’t work properly in almost all advanced prostate cancers, though cancer is complicated, and it’s known that PTEN does not work alone. In this project a revolutionary genetic tool is being used that can be used to alter hundreds if not thousands of genes at once to identify the other changes that occur when PTEN is ‘lost’. It is hoped that the approach can be used shortly to test new treatments and identify those that are most likely to work with fewer side effects.

MCL-1: a new therapy for prostate cancer?

MCL-1 is a protein which plays a key role in stopping cell death (called apoptosis), which is normally an essential process that keeps us healthy. It is known that high levels of MCL-1 can result in cells growing uncontrollably, leading to cancer. High levels of MCL-1 are found in men with advanced prostate cancer and high levels of MCL-1 are also thought to be linked to hormone therapy resistance. This protein has already been shown to be important for the development of other cancers, including breast cancer. However, we currently understand very little about MCL-1’s role in prostate cancer. It is hoped that this research project will establish the role that MCL-1 plays in prostate cancer. This will open new avenues for research into cancer that has spread, and for treatment resistance. In the long term, this will mean new ways to treat prostate cancer and improve outcomes for patients.

How fat fuels prostate cancer

We know that being overweight or obese may increase a person’s risk of developing aggressive prostate cancer, which means it will be more likely to spread and become life-threatening. Studies have shown that increased fat surrounding the prostate itself is linked to more aggressive disease and poor treatment response, but currently we understand remarkably little about how this fat promotes the disease. In this study, fat from around the prostate and tumour samples have been taken from men who are undergoing prostatectomy. The researchers hope to identify and compare the molecules in the samples from patients with and without obesity and explore how these molecules affect the behaviour of prostate cancer cells grown in the lab. Clinical data and information on diet and lifestyle will also be collected from these men. This will enable the researchers to find patterns between a person’s lifestyle and the aggressiveness of their prostate cancer in future studies. They hope to identify new drug targets and markers for aggressive disease.

More information on the work Prostate Cancer Research carry out can be found at www.pcr.org.uk.