CRIS PROGRAMME OF EXCELLENCE 2019
Introduction:
In developed countries, prostate cancer is the most commonly occurring tumour in males. Generally, most patients are diagnosed in the early stages when the tumour is still localized and are usually cured. However, in 5-10% of patients, diagnosis occurs when the tumour has already spread. Even among patients with localized tumours, some patients’ tumours are highly aggressive and resistant to standard therapies, which can lead to death. In the UK, every 45 minutes one man dies from prostate cancer – that’s more than 11,500 men every year.
It is vital to understand which patients are at a greater risk of aggressive and treatment-resistant forms of prostate cancer. At present, there are very few tools to predict this. If we understand which patients are at a greater risk, we can avoid using ineffective treatments and opt directly for other types of therapies, in addition to carrying out more extensive monitoring of their disease. This is the field of study in which Dr David Olmos’ group has been engaging for many years.
One of the group’s most relevant findings is that it has managed to relate the alterations (or absence) of some proteins that repair DNA with the development of much more aggressive forms of the disease. These proteins include BRCA2, whose alterations are a risk factor both for developing prostate cancer and for it becoming highly aggressive. Nonetheless, even in patients with BRCA2 mutations, their tumours differ greatly: they are more or less highly aggressive, they have a greater or poorer response to different therapies, a greater or lesser tendency to metastasise, etc. Therefore, still we have a long way to go before we can predict how prostate tumours will behave.
A recent finding of Dr Olmos’ group is that errors in another protein called RB1 (which controls appropriate cell division) may also relate to a poorer prognosis. In fact, it has been noted that in certain very fatal prostate tumours, alterations frequently appear in both genes, BRCA2 and RB1, concurrently.
However, almost nothing is known about the role of RB1 in prostate cancer, such as why it causes more aggressive tumours and how it contributes to BRCA2 mutations. Unsurprisingly, much less is known about how to target these alterations with therapies.
The project:
Dr Olmos’ team has designed a project to comprehensively address the problem of combined alterations in the BRCA2 and RB1 genes:
- Using advanced laboratory models, the biological mechanism that causes the two mutations combined to stimulate the appearance, growth and aggressiveness of prostate tumours is studied
- The team will develop methods for early identification, during diagnosis, of patients with this double alteration, in order to act sooner and more effectively
- With the help of innovative genetic modification techniques, the team will seek the best way to limit the devastating effects of the combination of BRCA2 and RB1 mutations and develop new treatments
In summary, the development of new ways to identify and treat these patients at such high risk of dying from prostate cancer has the potential to improve the lives of large numbers of patients.