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
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
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