Development of CD200 Stratified Kidney Cancer Immunotherapy
Dr Girish Patel, Cardiff University
Renal (kidney) cancer is the seventh most common cancer in the UK with around 12,000 new cases per year and unfortunately the likely outcome remains poor, with only a 50% 10-year survival. In some renal patients their own immune system can attack the cancer, resulting in a reduction of tumour growth. This has led to the development of treatments that aim to enhance these immune responses.
The discovery of specific markers that are known to influence the immune response to cancers have been identified and the presence of these markers have been found in abundance in renal cancer. The presence of one of these markers, known as CD200, has been shown to help the cancer hide from the immune system allowing it to grow. Using treatments that block the CD200 marker resulted in the immune system being able to attack the tumour resulting in a decrease in tumour growth. We would like to identify the presence of the CD200 marker in renal cancer patients and correlate this with the likely outcome and identify if there would be any therapeutic benefit to patients.
Spit and Save: Towards a saliva-based screen for the early detection of lung cancer
Professor Luis Mur, Aberystwyth University
Lung cancer (LC) is responsible for 1.3 million deaths each year. Despite several significant advances, only around 15% of patients have life expectancies greater than 5 years once diagnosed. Late detection is a major factor in this poor outcome as early symptoms are similar to those of other smoking related diseases.
This project will build upon previous studies from our research group, where several non-invasive biomarkers have been found for both LC status and stage. These biomarkers include changes in the chemical composition of saliva in LC patients.
This project will analyse the chemical composition and protein content of saliva samples from LC patients and a control population to confirm biomarkers which have already been identified and search for new protein biomarkers.
Our ultimate aim as a group is to use these biomarkers to develop a safe, non-invasive test, which could accurately diagnose and predict treatment responsiveness, potential for disease spread, and prognosis. If successful, our studies could effectively inform and change clinical practice in the near future.
Development of Personalised treatment in Ovarian and Colorectal Cancer
Dr Karen Keating, Almac Diagnostics
Almac have discovered and validated two molecular signatures to support personalised treatment in breast and ovarian cancer, namely the DNA Damage Repair Deficiency (DDRD) and Almac Angiogenesis (AADx) assays, respectively. The DDRD Assay identifies breast cancer patients that are likely to benefit from DNA damaging chemotherapies and the AADx assay identifies a subgroup of high grade serous ovarian cancer (HGSOC) patients that have superior survival on standard of care chemotherapy. The aims of this study are to expand the utility of the AADx assay into the neo-adjuvant treatment setting of ovarian cancer and to evaluate both signatures in the metastatic colorectal cancer (mCRC)setting.
Generation of breast cancer organoids
Professor Trevor Dale, Cardiff University
Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million cases diagnosed in 2012. Cancers of the breast are notoriously difficult to treat and there remains substantial need for the basic research required to support the discovery of improved and targeted therapies and minimise adverse side-effects.
Our group has a history of patient derived cancer model development using 3D cell cultures called organoids. Organoids are miniature organs grown in 3D that preserve the original architecture, composition and function of cell types present in the original tissue. There is accumulating evidence that organoids better predict drug efficacy than the 2D cell lines currently used since they replicate key aspects of human tumours. Until recently, organoids could only be grown laboriously on a small scale, however our collaboration with Cellesce (a biotechnology company spun-out of Cardiff and Bath Universities), has enabled the expansion of colorectal cancer organoids on a suitable scale for drug screening using specific conditions in a bioreactor. This project seeks to collect patient breast tumour material and to produce reliable organoid models, and characterise their drug responses to compare to clinical treatment data. The use of breast organoid models will potentially revolutionise pre-clinical screening
Development of Automated Technology for use in Clinical Pathology
Dr P Hamilton, Philips Digital
The reason behind our need for lung slides is an ongoing research program into the automatic identification of tumor on histological slides (Initially Lung NSCLC). Slides will be scanned at 40x on the Philips slide scanner. The resultant image will form the basis for the application of image analysis techniques to identify tumor via a boundary. This would be achieved by training a classifier to distinguish between tumor and non-tumor. This mark-up can be used to suggest a region of the case which is suitable for macro-dissection purposes. We would propose to acquire a large cohort of lung cases (initially) for training and validation.
This algorithm we propose can be rolled out across many tissue types and we currently have a need for lung, colorectal, breast, prostate and ovarian tissues (we are currently focusing on lung initially). We would be hoping to get somewhere between 1000 – 3000 slides per tissue type (not all from a single source) which would will require 100+ slides from each organization. Suffice to say we are looking for large amounts of cases.
Validation of a Novel Compound for the Treatment of Prostate cancer
Dr R Clarkson, Cardiff University
We have developed a novel experimental anti-cancer agent that evidence suggests would be particularly effective at treating prostate cancer patients who have a high risk of their tumour spreading to other parts of their body. In order to confirm this we propose to test the novel agent (OH14) on tumours taken directly from prostate cancer sufferers, to determine if this agent works in the near clinical setting. If it does, we will establish which tumour types are most sensitive to the treatment, and whether this agent also improves the efficacy of existing therapeutics that are currently used in the clinic. This study will involve the establishment of a new supply route of fresh prostate tumour tissue to be grown from prostate cancer patients and maintained in the laboratory in Cardiff. Optimising and establishing this pipeline of fresh prostate cancer material will be a valuable technique for the prostate cancer research community.
Exploring Drug Resistance in ER+ Breast Cancer
Prof W J Griffiths, Swansea University
In 2011, just under 50,000 women were diagnosed with breast cancer (BC) in the UK, of which about 70% are classified as estrogen receptor α positive (ER+). This means they produce high levels of a particular protein called the “estrogen receptor α” (ERα) in cancer tissue. People with ER+ BC respond well to existing drug treatments. Despite this, however, a complete cure for ER+ BC is hindered by the body becoming resistant to drug therapy over time and the cancer may reoccur after 5 years of drug treatment.
For ERα to have harmful effects in tissue and promote BC it needs to be “turned-on” by a small molecule. The sex hormone 17β-estradiol can activate ERα and the class of BC drugs called aromatase inhibitors stop the production of 17β-estradiol in postmenopausal women, this means that less 17β-estradiol is available to stimulate the growth of ER+ BC cells. New research from America suggests that other small molecules made by the body may also activate ERα and trigger BC even in people undergoing aromatase inhibitor treatment.
We hypothesise that these small molecules, called hydroxycholesterols, may explain the resistance to drug therapy in some people with ER+ BC. In this study we will test the hypothesis by analysing blood serum from people with BC and people without BC and determine the concentrations of hydroxycholesterols. Results from this study will improve our understanding of ER+ BC and give hints towards new drug treatments.
How Stress can effect response to Chemotherapy in Triple Negative Breast Cancer
Dr M Flint, Brighton University
Stress hormones have been shown to reduce the effectiveness of chemotherapy drugs commonly used to treat one of the more aggressive types of breast cancer - Triple Negative Breast Cancer. Some changes in DNA (the building blocks of cells) are thought to affect the bodies’ response to stress and so our goal is to determine whether one of the most common changes in DNA makes a patient less likely to respond well to treatment.
We intend to find out how common the DNA variation is in Triple Negative Breast Cancer patients by examining breast tumour tissue and comparing our findings to the treatments and outcome of the patients. We would like to be able to predict a patients’ response to chemotherapy and determine whether medications to reduce stress or therapies, such as meditation (which also reduce stress) may improve treatment outcome, experience and survival prospects.’