Research showcased by our scientists could lead to targeted prostate cancer therapies

Scientists funded by Prostate Cancer UK have been inspiring the next generation of researchers with exciting results in genetics and nanoparticle treatment. Our Blue skies forum, supported by the Howard Foundation, brought together 300 scientists, doctors, nurses and students to discuss the very latest prostate cancer research. Some of the best minds working in the area presented findings from their research projects, three of whom we are supporting. The event, which took place in Cambridge in April, was both a call to arms for young scientists and an opportunity for the research community to discuss their plans to tackle prostate cancer.

Headline-grabbing breakthroughs in genetics

Professor Ros Eeles, a Professor of Oncogenetics at The Institute of Cancer Research presented research that will help us to identify which patients have high-risk prostate cancer, meaning disease that is likely to progress and should be treated.  Professor Eeles is part of The PRACTICAL consortium, which is made up of 61 research groups around the world.

The researchers looked at the DNA of over 25,000 patients with prostate cancer and the same number of men without the disease.  They were able to identify 23 new genes associated with prostate cancer, and discovered that 16 of these are linked to aggressive prostate cancer. This information will be used not only to identify patients at risk but also to develop new drugs that can target specific genetic changes in these patients.  Research is still ongoing in these areas and the genetics of men with a family history of prostate cancer are also being investigated.

Professor Eeles also discussed her work on mutations in the BRCA1 and BRCA2 genes, both of which have been grabbing news headlines recently. Mutations in the BRCA2 gene increase the risk of prostate cancer by 8.6 times in men aged 65 years and over and mutations in the BRCA1 gene increase the risk by 3.7 times.  Also, mutations in the BRCA 2 gene mean that the prostate cancer is more aggressive and is more likely to spread, resulting in a worse outcome for the patient.

New research is exploring in more detail how these mutations are linked with the stage of the disease and if the disease is present in the lymph nodes or elsewhere in the body. Researchers have found that patients survive longer if they do not have the mutations compared with those who do (15.7 v 8.6 years).

Male hormones and prostate cancer growth  

Professor David Neal, a Professor and Surgical Director of Clinical Oncology from Addenbrooke's Hospital in Cambridge, discussed the work that he and other researchers are doing into the role of the androgen receptor in prostate cancer growth.

Androgens are male hormones (commonly known as testosterone) that can stimulate prostate cancer cells to grow and they are blocked by hormone therapy treatment. The androgens bind to the androgen receptor and that binds to the DNA in prostate cells. This in turn makes tumours grow. Researchers are looking at where the androgen receptor binds to the DNA in a prostate cell. And through DNA sequencing (determining the order of the building blocks that make up DNA) they have identified a number of genes involved in this process. These results will be important for developing new drugs that target these genes and so far one drug, STO-609, has already been shown to inhibit prostate cancer growth.

The androgen receptor acts in a different way once a man with prostate cancer has stopped responding to hormone therapy, and begins to make tumours grow independently of the presence of androgen. Further research is looking in more detail at what changes take place to the androgen receptor which allow it to become active in tumour cells in the absence of male hormones. So far, 16 genes have been identified that are more active in these patients. These genes will again be possible targets for future therapy.  

Mr Hashim U Ahmed, a Clinical Lecturer in Urology from University College London, talked about his research into a focal therapy for prostate cancer. Focal therapy is a treatment in which only the part of the prostate that contains a tumour is treated. This could be used in patients who have very little tumour as well as those patients whose disease is unlikely to spread outside the prostate. A number of treatments can be used in focal therapy, such as cryosurgery, HIFU (high intensity focused ultrasound), photodynamic therapy, radiofrequency interstitial tumour ablation, brachytherapy and mixed ablation.  There are several published studies on the results. Overall, there were few complications and side-effects but it was hard to measure how well the treatment controlled the disease. More studies are now underway with the UK leading many of these.

New nanoparticle treatment

Mr Ahmed's team in London are testing a new focal treatment called magnetic nanoparticle thermoablation that could be used in men with prostate cancer that has not spread outside the prostate (localised prostate cancer). The treatment involves injecting iron oxide into the prostate and then applying an alternating current in a magnetic field. This causes the prostate tissue to heat up to around 45°C, which kills the cells. The longer the magnetic field is applied the higher the temperature reached.

So far, the treatment has been given to 10 patients in whom other treatments have failed. These patients received six thermal therapies for 60 minutes each at weekly intervals using an alternating magnetic field applicator. Maximum temperatures up to 55°C were achieved in the prostates; urethral and rectal temperatures were 40.5°C and 39.8°C, respectively. CT (computed tomography) scans showed that the iron oxide particles stayed within the prostate, which is very important to avoid damaging other tissues.

The next study will test the treatment in 108 men just before they undergo radical prostatectomy. Nanoparticles will be injected into their prostates and scans will be done to check whether the there are enough particles to reach a temperature that is likely to be effective (70°C). After this, studies will look at the damage caused to the prostate tissues following treatment.

The studies discussed at the Blue skies forum are just a sample of some of the work currently taking place in the UK to help more men survive prostate cancer. With the help of Movember, we are investing £25 million into new research over the next three years. And in order to continue getting (and keeping) the next generation of scientists and researchers interested in prostate cancer research, we are funding a number of training and development awards. Hopefully many of the men and women in the audience at this year's Blue Skies Forum will be the next Ros Eeles, David Neal or Hashim Ahmed - leaders of their field in the fight against prostate cancer.

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