Targeted Cancer Therapy
The largest single group within the Cardiovascular and Cancer research group is headed by Professor Hardev Pandha and is based at the Leggett building (formerly the Postgraduate Medical School). This research group have access to state of the art laboratories and are conducting cutting edge research into targeted therapies for cancer, diagnostic biomarkers to detect prostate cancer from patient urine and also biomarkers which will aid diagnosis and prognosis of prostate cancer.
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 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.
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.
EN2 viral vaccine
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.
Novel therapeutic strategies for castrate resistant prostate cancer (CRPC)
Research into the identification of molecular/cellular mechanisms that lead to the development of castrate resistant prostate cancer (CRPC). In particular the development of therapeutic strategies to inhibit the oncogenic transcription factor the Androgen Receptor (AR) which is the major driver of the disease with an overall goal to eradicate CRPC or delay its onset.
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.
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
The Sun Study
- Complete a bio-repository and accompanying ‘database’ of 300 patients with all stages of prostate cancer to allow longitudinal blood sampling whilst on different treatment programs, and enable banking and analysis of serum and DNA at 6 monthly intervals. This group is unique in that it comprises an almost homogenous population of Caucasian patients, most of who won’t move out of the area (allowing long term follow up).
- Using the SUN study population, we will identify proteins in the blood serum which are characteristic for prostate cancer in comparison with benign disease (those patients found not to harbour cancer after prostatic biopsy, will be aged matched controls), using sophisticated cutting edge methods of protein analysis.
- We will identify changes in biomarker profile depending on the cancer stage and cancer grade in newly diagnosed cancer following radical treatment, in patients on hormonal treatment, in patients with hormone – resistant disease and in patients with widespread disease.
- We are currently setting up an ethnic Sun Study to look at the differences in biomarkers between the afro-caribean population, who have a very high incidence of prostate cancer, and the caucasian population.
This resource is available to researchers internationally and we are pleased to announce that we are now members of National Cancer Research Institute’s Confederation of Cancer Biobanks (CCB). CCB is a consortium of organisations based in the UK that are involved in the development, management and use of biobank resources for cancer research. Please contact Dr Agnieszka Michael for further details.
Dr Hardev Pandha, Dr Mazhar Ajaz and Dr Agnieszka Michael
A clinical team of 12 staff are developing a large programme of clinical research directed at improved treatment for cancer, understanding the causes of cancer and developing new methods of detection.
For further details of our currently running clinical trials please see the Surrey, West Sussex and Hampshire Cancer Network.
|Dr Nicola Annels||Research Fellow||01483 68 email@example.com||09 PGM 02|
|Mr Mick Denyer||Laboratory Technician||01483 68 firstname.lastname@example.org||07 PGM 00|
|Dr Mohammad Asim||Lecturer in Molecular Cancer Biologyemail@example.com|
|Mrs Wendy Hobby||PA to Professor Hardev Pandha||01483 68 firstname.lastname@example.org||26 PGM 02|
|Professor Hardev Pandha||Professor of Medical Oncology||01483 68 email@example.com||26 PGM 02|
|Dr Kate Relph||Postdoctoral Reseach Fellow||01483 68 firstname.lastname@example.org||07 PGM 02|
|Dr Guy Simpson||Research Fellow Oncology||01483 68 email@example.com||30 PGM 02|