Prostate Cancer Research
Prostate cancer is the leading malignancy of men in Wales, with approximately 2,400 new cases diagnosed each year.
Cancer Research Wales has a committed prostate cancer research programme, of which the overall aims are:
- Decipher the mechanisms of how prostate tumours develop new blood vessels (angiogenesis) to support tumour growth and spread.
- Identify novel ways to limit the process of angiogenesis (tumour blood vessel formation).
- Investigate the role that prostate cancer exosomes play in promoting angiogenesis and immune evasion.
- Understand how the immune system influences prostate cancer development and progression to help inform current clinical trials that involve novel immuno-therapies.
The growth of tumour blood vessels, a process known as angiogenesis, provides a continual supply of nutrients and oxygen to dividing cancer cells. These blood vessels also provide a route by which detached cancer cells can spread around the body to form secondary tumours. Research funded by CRW is finding ways in which to disrupt the process of angiogenesis in prostate cancer. Scientists have discovered that a hormone-like substance called Hepatocyte Growth Factor (HGF), acts as a driver of new blood vessel formation in prostate tumours. HGF is found to significantly elevate the levels of two molecules, TEM-8 and CMG2, both critical for the generation of fully functional tumour blood vessels.
Based on these findings, a series of peptide inhibitors that can specifically bind and disrupt these molecules have been developed. These inhibitors remarkably impede the formation of blood vessels in preclinical models of prostate cancer angiogenesis. Importantly, these inhibitory peptides serve as a template from which medicinal chemists are able to design small organic molecules that mimic their action (mimetics) for the development of new drugs that can be taken forward for clinical evaluation.
Other research based at the CRW laboratories within the grounds of the Velindre Cancer Centre is looking at biological structures called exosomes. These are well organized bodies of lipid (fats) and chemicals that are secreted by prostate cancers. An emerging function of prostatic exosomes is their ability to trigger blood vessel formation, via a collection of growth factors contained within their membranes. Ongoing work is seeking exciting ways in which to prevent the release of exosomes from prostate cancer in order to prevent angiogenesis and limit the growth and spread of prostate cancer.
CRW scientists are also providing vital insights into the processes that govern immunological responses in prostate cancer patients. In addition to their ability to promote the formation of tumour blood vessels, exosomes have also been discovered to induce immune evasion. One mode of action occurs via enzymes that are strategically positioned on the outside of exosomes. These enzymes produce important immuno-suppressive and anti-inflammatory molecules that are released within the immediate tumour environment to suppress anti-tumour immune cells. Exosomes also appear to blunt the response of immune cells to IL-2, an important immune system messenger that is vital for the stimulation of a fully functional immune system.
Several high-profile clinical trials have shown that immuno-therapy, mainly in the form of cancer vaccines can prolong survival in some prostate cancer patients with advanced and treatment resistant disease. Important questions have arisen from these studies, including the correct timing and scheduling of immuno-therapies within the treatment pathway. On this note, scientists at the CRW laboratories have discovered that radiation beams can significantly stimulate key anti-tumour immune cells, whose activities had been suppressed by tumour related processes within patients. These exciting findings point to previously unrecognised roles for radiotherapy in prostate cancer and reveal unique windows of opportunity that can be exploited by immuno-therapy to further improve survival
Cancer Research Wales aims to reduce the impact of cancer on the people of Wales through supporting world class cancer research and education. Because around 2,500 men are diagnosed with prostate cancer in Wales each year, at CRW we believe it is important to:-
- Understand the cellular pathology of prostate cancer and discover new treatments that can specifically target these defects.
- Improve the effectiveness of existing treatments and newer immuno-therapies.
- Reduce the risk and burden of metastasis.