Research
Projects 2011-12
Dr Patrick Pollard — Metabolic transformation in hereditary renal cancer: Identification of novel pathways and targets
Normal cells have the potential to undergo transformation into cancer cells. During this process, the cells undergo changes both in metabolism and in the expression of genes which encode proteins that help facilitate the growth of solid tumours.
Dr Pollard and his team have generated cells which mimic this defect in order to analyse changes in metabolism and gene expression that may contribute to cellular transformation and cancer. Such information will be used to identify targets amenable to therapeutic intervention in hereditary and other renal cancer types.
Dr Val Macaulay —A screen for proteins that influence sensitivity to IGF-1R inhibition
This project focuses on a protein called IGF-1R, present at high levels in prostate cancers.
The IGF-1R stimulates growth of prostate cancer cells, making it an attractive target for cancer treatment. IGF-1R blocking drugs are being tested clinically; some tumours respond dramatically, but others show no response. At present we know little about what makes tumours sensitive to IGF-1R blockers, nor how best to combine these drugs with other treatments.
We hope this project will tell us what makes prostate cancers sensitive to IGF-1R blockers, and help us to design clinical trials of combination treatments for prostate cancer.
Mr Chris Blick — Mechanisms of response and resistance to therapeutic agents in renal cell cancer.
Approximately 8000 kidney cancers are diagnosed in the UK/year. Due to the late onset of symptoms and the lack of available screening tests >25% of kidney cancers are non-curable at the time of diagnosis.
A number of therapies are currently available which target molecular pathways involved in cancer growth. These have improved patient outlook but many tumours fail to respond or develop resistance to treatment.
The reasons for varied success are currently unclear, kidney cancer is a complex disease and variations in gene activation amongst different tumours exist. Another possible explanation is the failure of therapies to target cancer stem cells (CSCs). Recent evidence suggests that solid tumours contain a subpopulation of CSCs. CSCs have the ability to initiate and continue growth, the incomplete eradication of these cells may explain late recurrence and metastasis.
We have successfully cultured a number of kidney cancers removed from patients at the time of surgery and assessed their dose response to various drugs. We aim to analyse and profile the genetic differences of these tumours and compare that to the response of these cells to treatment with current therapies. We also aim to isolate stem cell populations from cancer cell lines and investigate the differences in response to drug treatment when compared to that of the general cell population. Isolating molecular differences which can predict drug sensitivity in cancer is a stepping stone on the path to achieving personalised medicine.
Isha Prematilleke — Lymphovascular invastion in testicular seminomas
Seminoma is a malignant tumour arising in the testis. It is the commonest tumour of the testis and most often spreads to the lymph nodes first. The presence of such metastasis influences management and outcome for the patient. Detection of tumour within lymphatic vessels of the testis by the pathologist is a predictor of the possibility of spread to lymph nodes. It is therefore important that such detection be made accurately. The presence of lymphovascular invasion can be difficult to assess using routine histopathological stains and criteria for its diagnosis have not been defined. There is a high interobserver variation in its diagnosis. Immunohistochemical stains are not routinely used to identify vessels in the assessment of lymphovascular invasion.
D2-40 is an immunohistochemical stain which picks up the lining of lymphatic vessels, as well as stains the seminoma (tumour) cells themselves. In practice it has been observed that it is easier to pick up lymphatic invasion by tumour cells using this stain. This project aims to quantify the improvement in detection of lymphovascular invasion using D2-40 staining, and correlate it to clinical outcome in these patients, in order to investigate whether routine performance of this technique to detect lymphatic invasion should be recommended to improve outcome.
Previously supported projects
2009-2011
Biobank Research Nurse
In 2009, UCARE made a grant to support a bio-bank research nurse.
Working as part of a multi-disciplinary team the nurse will promote trials and facilitate high quality research. The nurse will provide practical information and vital support, and in the same setting, will assist research doctors with recruitment and monitoring of patients and data collection. Also, the nurse will facilitate the collection of tissue samples for laboratory research [bio-banking] which allows for a wide range of analyses to give a better understanding of the genetic and molecular changes involved in the progression of cancer and can also be used for assessing the effectiveness of novel drugs and therapeutics.
The role of the specialist cancer research nurse is growing in importance and stature in hospitals throughout the UK as they are at the forefront of cancer care in a role that combines the challenging mix of patient contact and clinical research activities. This post is vital to the advance of Urology research trials in Oxford and we will be supporting this for a further year (2010-2011).
2008-2011
Research Scientist
UCARE's largest grants have supported the work of Dr Val Macaulay and her research team, who are developing clinical trials for an exciting new anti-cancer treatment. We have made grants to this project in 2008-2009; 2009-2010 and for a further year 2010-2011.
Dr Macaulay (Senior Clinical Research Fellow and Honorary Consultant in Medical Oncology) leads a research team at the internationally renowned Weatherall Institute of Molecular Medicine. The team studies the function of a cellular protein which is vital to the survival of cancer cells in the prostate, bladder and kidney.
Dr Macaulay and the team are now testing the potential therapeutic benefits of inhibiting the “cancer creating” function of this protein. In response to this and other research findings some major pharmaceutical companies have created drugs to do just this and Dr Macaulay wants to begin clinical trials in Oxford to test the efficacy of these drugs. This research project is designed to discover a treatment for prostate, kidney and bladder cancers that have not responded to traditional surgery, chemotherapy and radiotherapy treatments.
“I am delighted to have joined Dr Macaulay's team, so that we can move forward with the development of a new treatment for patients with urological cancers. I am very grateful for the generous donations that have funded this job.” Olga Perestenko, October 2008
“Thanks to the generosity of UCARE supporters, Olga has been running my research lab for the past 2 years, with a commitment from the UCARE Trustees to fund a third year as well, from October 2010. Olga has a dual role, as Research Scientist and Laboratory Manager. She is contributing to three vital areas of work, all focused on a new cancer treatment that blocks a growth-promoting protein called IGFR. Firstly, Olga is developing tests that we can use to monitor new IGFR-blocking drugs, which we are now evaluating in cancer patients. Secondly, Olga has developed a way of taking a small piece of kidney cancer from a kidney removed at operation, and growing the kidney cancer cells in the lab. This will help us to understand what makes some cancers sensitive or resistant to new cancer drugs. Thirdly, in her role as Lab Manager, Olga has organised the lab and made searchable inventories of all our stocks, so improving the efficiency of everyone in my group. I am so grateful for this support from UCARE, which is making a huge difference to our progress in improving treatment options for patients with urological cancers.” Dr Val Macaulay, August 2010
