Research funded by the Prostate Project Foundation
The Prostate Project funds The Prostate Project Foundation which gives financial support to the Oncology team which is based in The Leggett building (formerly Postgraduate Medical School) at the University of Surrey. The Leggett building is located on a site 10 minutes from main campus situated next to The Royal Surrey County Hospital and the Surrey Clinical Research Centre (CRC). This internationally acclaimed group is led by Professor Hardev Pandha who is also a Trustee of our charity. The group has access to state of the art laboratories and the close proximity to the hospital and CRC facilitates translational research and clinical trials. The research group are conducting cutting edge research in both these areas including targeted therapies for cancer, diagnostic biomarkers to detect prostate cancer from patient urine and also biomarkers which will aid diagnosis and prognosis of cancer. The Prostate Project was pivotal in the creation of this group providing 50% of the start-up funding.
The scientists at Guildford have access to invaluable resources that other cancer research centres find difficult to access. This is due to close collaborative relationships that exist between the clinicians, scientists and laboratories at the Leggett Building. This combination brings to the decision-making process the views of patients, medical experts and researchers which is resulting in significantly shorter leadtimes for diagnosis and treatment
Key Achievements So Far by the Research Team
- Development of a unique diagnostic urine test for prostate cancer
- Identification of a novel protein, HXR9, which targets cancer cells and causes them to self destruct
- Development of a novel peptide agent, HWFT, to enhance cancer vaccine efficacy.
- Establishment of the SUN study – a bio-repository and accompanying ‘database’ of 450 patients with all stages of prostate cancer.
- Clinical Trials involving cutting edge new agents
- 80 publication in peer reviewed journals and a new text book ‘Viral Therapy of Cancer’
- National and international collaborations
- 5 Patents filed
To find out more about the Oncology research team at the Leggett Building, visit: http://www2.surrey.ac.uk/pgms/research/cancer/
Current research projects by the team:
1. Biomarkers including the Sun Study Dr Aggie Michael
PSA is an important and useful test for prostate cancer. However, its use is limited by the fact that PSA levels also increase in non-cancerous conditions of the prostate.
We have discovered that the EN2 protein is highly expressed in prostate cancer and that prostate cancer cells export EN2 into urine. Importantly, the amount of EN2 in urine can provide information about how large a tumour is. We have published our work in the journals Clinical Cancer Research and British Journal of urology, and we have received widespread publicity in the media. Work is ongoing to improve the accuracy of the test and address its potential in diagnosis and surveillance.
Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer.
Pandha H, Sorensen KD, Orntoft TF, Langley S, Hoyer S, Borre M, Morgan R. BJU Int. 2012 Sep;110(6 Pt B):E287-92
Engrailed-2 (EN2): A Tumor Specific Urinary Biomarker for the Early Diagnosis of Prostate Cancer. Morgan R, Boxall A, Bhatt A, Bailey M, Hindley R, Langley S, Whitaker HC, Neal DE, Ismail M, Whitaker H, Annels N, Michael A, Pandha H. Clin Cancer Res. 2011 Mar 1;17(5):1090-8
BBC NEWS 1st MARCH 2011
SKY NEWS 1st MARCH 2011
WOMEN'S HOUR BBC RADIO 4 13th JUNE 2011
2. Embryonic Gene Targeting - Dr Richard Morgan
Potential targets for novel therapies include proteins involved in cell growth and signalling within the cell. These include proteins, so called transcription factors, that have previously been identified as being switched on in cancer and therefore lead to unchecked growth of cells. Of particular note are the HOX genes, a family of proteins normally involved in development of the nervous system in the embryo. We have designed a small protein, HXR9, which is able to pass into the cell and disrupt the interaction between HOX and a second protein, PBX This protein is able to cause cell death when added to cancer cells in culture and also can also reduce or prevent the growth of melanoma, breast, lung, ovarian and prostate tumours. We hope to develop this protein further for use as a therapy for cancer.
3. Viral and Gene Therapy of Cancer - Dr Guy Simpson
In recent years viruses have been widely investigated in scientific research for their use as novel therapies for disease. We are investigating both herpes simplex virus (HSV) and reovirus in bladder and prostate models. Reovirus is able to replicate within tumour cells and not in normal healthy cells of the body due to a specific mutation of a gene common to many cancers. As the virus replicates within the tumour cells new viral offspring are produced. These burst out of the cell causing the tumour cell to burst and die. We are studying the ability of reovirus to kill a variety of tumour cell types and, more specifically, the ability of reovirus to work in conjunction with conventional chemotherapy in prostate tumour cells.
4. EN2 - Dr Nicola Annels
The team’s work has shown that in addition to prostate cancer EN2 has been shown to be expressed in other cancers such as ovarian cancer and melanoma. EN2 is a unique target:
- EN2 is a novel target and has never been used before
- There are several possible routes to targeting EN2 that can be explored (see below)
- There is an unmet need for the development of immunotherapeutics which use the body’s own immune system to target only tumour cells leaving normal cells untouched. This means a much more efficient therapy and fewer side effects for the patient.
EN2 as an immunotherapy for Cancer
We aim to investigate whether a patient’s own immune system can mount an immune response to EN2. The presence of these so called autoantibodies, which are produced in response to abnormal proteins on the surface of tumour cells e.g. EN2, may be detected in the early stages of cancer and/or used as a monitoring tool.
In cancer therapy, antibodies can be raised against specific proteins present on the surface of tumours. A good example is the Herceptin antibody for breast cancer which targets the Her2neu cancer gene displayed on the cell surface (in an identical way that EN2 is displayed)
We will develop antibodies specific for EN2 which can be linked to toxic compounds and used as targeted therapy.
We will generate a panel of antibodies specific for EN2 and test their ability to cause cancer cell death using animal models. We will check the targeting of the EN2-specific antibodies using a special camera and further confirm their location using tissue staining.
A number of viruses provoke the immune system. These viruses have been modified and rendered safe, but are extremely efficient at stimulating anti-cancer immunity in patients.
We have shown that the immune system can be ‘educated’ to see cancer cells and kill them. This may be achieved with high efficiency using a virus. We will use a virus to generate immunity against EN2 and test it in an animal model. As we know EN2 is only made by cancer cells, normal cells and tissue should be spared.
We will aim to use the labelled antibodies to EN2 to allow us to image tumours expressing EN2 on their surfaces. As EN2 is only made by cancer cells, we should be able to define even small tumour deposits with a high degree of accuracy. We will test this concept in animal models but if successful this will be a novel imaging method which will also allow us to monitor the size of patients tumours and therefore monitor the progress of patients after treatments.
The success of these projects depends on your support
This research is hugely expensive, requiring long term investment. The charity relies almost totally on the generosity of it's supporters. Everyone involved is very conscious that all donations to this appeal should be used in full and have one ultimate goal - to bring direct benefits to prostate cancer sufferers and their families.
If you can make a donation or are in a position to help us in any way, please contact:
Colin Stokes, Chairman
Tel: 01483 419501