Melanoma or skin cancer is one of the fastest rising cancer types. When identified early, melanoma is relatively easy to cure, but once it starts to metastasise, it becomes very difficult to treat. DEREGULATION OF TRANSCRIPTION The interface between signal transduction and transcription regulation coordinates gene expression. Deregulation of transcription is a key factor in cancer. Professor Colin Goding studies how a precise programme of transcription regulation is achieved, particularly in the transition between normal and cancer stem cells, and the parallels with normal stem cell populations.

Cancer

Melanoma

Transcription is a tightly regulated process, where chemical modifications initiate the duplication of genetic material. This epigenetic process is often dysregulated in cancer, but it can be targeted with small molecule inhibitors. EPIGENETIC SIGNALLING Professor Panagis Filippakopoulos is interested in the molecular mechanisms of transcription, where the formation of non-covalent protein complexes is mediated by post-translational modifications. Dysfunction in this epigenetic signalling process is linked to disease, particularly cancer.

Targeting epigenetics to treat cancer

Dr Gareth Bond, Associate Member of the Ludwig Institute for Cancer Research, studies the influence of genetic variants on the origins, progression and treatment of human cancer. SNP - single nucleotide polymorphisms There is great heterogeneity between individuals in their risk of developing cancer, disease progression and responses to therapy. Specific single nucleotide polymorphisms (SNPs) are associated with human cancers. They have the potential to help us identify individuals more at risk of developing cancer, and better target preventative or therapeutic strategies.

Human Cancer Genetics

Dr Jenny Taylor is the Programme Director for the Genomic Medicine Theme, Wellcome Trust Centre for Human Genetics. Her research bridges the gap between genetics research and the use of its discoveries in diagnosis or treatment of medical conditions. Clinical diagnoses can be broad descriptions, but today's test results can help better understand the condition as well as target treatment. Cancer is a good example in which personalised medicine can help decide which molecular targeted therapy is most appropriate.

Personalised Medicine

Identifying genes that increase the risk of bowel or other cancers allows us to offer preventative measures, such as removing tumours at an early stage. A better understanding of how and why cancers grow also helps develop improved treatments. Ian Tomlinson, Professor of Molecular and Population Genetics at the Wellcome Trust for Human Genetics, works on the identification of genes that predispose to colorectal and other cancers. His research focuses on the relative importance of selection and genomic instability.

Cancer predisposition and evolution

Cancer research now generates huge amounts of data, and sophisticated computational tools are needed to answer biological questions. Making sense of this variability at molecular level will help us better tailor treatments to individual cancer patients. Dr Benjamin Schuster-Böckler heads the computational group at the Ludwig Institute for Cancer Research. His work has demonstrated that epigenetic modifications influence the mutational landscape in cancer cells. He studies the effects of DNA-binding proteins on transcription factors, with the aim to understand the regulation (and mis-regulation) of the transcription of important oncogenes and tumour suppressors.

Cancer Informatics

Professor Vincenzo Cerundolo tells us how research in immunology leads to the development of new cancer treatments. Immunotherapy stimulates the body's immune system, and can be a powerful treatment for cancer. The most efficient prophylactic cancer vaccine today is the vaccine against papilloma virus, whereas the development of therapeutic vaccines is more challenging. With the aim of developing better treatment strategies for cancer patients, Professor Vincenzo Cerundolo is working to gain a better understanding of the cell-to-cell interplay required for optimal expansion and activation of tumour-specific T cell populations.

Cancer Immunlogy

Professor Xin Lu talks about the links between cancer and regenerative medicine. Identifying the switches that turn cell growth off and on would have profound implications for cancer medicine. If the right mechanisms can be found, cancer cells could be targeted specifically, resulting in more efficient treatments. Professor Xin Lu is working to identify the molecular mechanisms that naturally suppress tumour growth. Nuclear reprogramming could also enable cells to be utilized more safely and effectively in regenerative medicine.

Cancer and regenerative medicine

Dr Raghib Ali talks about INDOX, the cancer research network in India. The INDOX Cancer Research Network is a collaboration between Oxford and twelve leading cancer centres in India. As Director of this Network, Dr Raghib Ali aims to improve early detection of cancer and to develop effective and affordable cancer treatments for low and middle-income countries. Dr Ali's main interest is in colorectal (bowel) cancer and other chronic, non-communicable diseases. Incidence of colorectal cancer in India has been relatively low historically; understanding why may help us establish risk factors and also lead to new treatments.

INDOX Cancer Research NetworK

Dr Patrick Pollard tells us about his research on cancer metabolism. Cancer cells produce energy predominately through a high rate of glycolysis; it has been suggested that this change in metabolism is the fundamental cause of cancer. Dr Patrick Pollard aims to elucidate the alternative metabolic strategies used by cancer cells with high concentrations of glucose to proliferate, even under conditions of stress. These mechanisms could then become targets for more effective cancer therapies.

Cancer Metabolism

Dr Opher Gileadi tells us how cells maintain genome integrity and how we can use it in our fight against cancer. While cigarette smoke and sun exposure can lead to DNA damage, which causes cancer, there are a number of natural processes within the body that can also lead to cell mutations. Dr Opher Gileadi studies the structure and chemical biology of the proteins involved in DNA repair and in recovery from DNA damage. Since DNA damage can be both a cause of cancer and a tool in fighting cancer, Dr Gileadi aims to uncover ways to better target and destroy cancer cells.

Genome Integrity

Professor Chris Pugh tells us about the links between genetics, renal disease and oxygen sensing. The kidney plays a central role in our metabolism, by controlling various physiological balances. Genetics is central to these mechanisms, since gene defects lead to all sorts of malfunctions. Oxygen sensing mechanisms were first discovered as a result of studies on the production of the kidney hormone erythropoietin. We now know that the underlying system controls about 1000 genes. Professor Chris Pugh is working on the oxygen sensing functions of the body to assist in designing better therapies for disorders that involve oxygenation problems, such as angina and cancer.

Renal Disease

Dr Bee Wee tells us about Palliative Care in Oxford and her research on end of life care and fatigue. Due to advances in medicine prolonging the lives of those with progressive, life limiting diseases, the need for long-term palliative care has increased. Dr Bee Wee is currently researching end of life care for people with incurable cancer and advanced non-malignant disease, symptom management and rehabilitation, to improve quality of life for patients. Dr Wee is the Head of Palliative Care Research and Development, based at Sir Michael Sobell House in Oxford.

Palliative Care

Professor Yvonne Jones talks about cell-cell communication and how this can help us develop new drugs. Cells communicate through receptors on their surface; however, when these finely tuned systems don't work correctly, diseases can be triggered. Professor Yvonne Jones has been working to identify the structural biology of cell surface recognition and signalling complexes. Receptors embedded in the surface are potential targets for therapeutic intervention in many diseases including cancer. Professor Jones is director of the Cancer Research UK Receptor Structure Research Group.

Cancer and Protein Crystallography

Professor Tim Key tells us about the role of life style and diet in the development of cancer. Although smoking is still the most important cause of cancer, we now know that obesity and high intakes of alcohol can increase the risk of several types of cancer. Professor Tim Key is researching the role of diet and hormones in the development of cancer, particularly cancers of the breast, prostate and bowel. Professor Key is the principal investigator of the EPIC-Oxford cohort of sixty thousand participants, for various studies on cancer, hormones and nutrition.

Role of Lifestyle and Diet in Cancer

Cancer is studied from several angles at NDM, from its epidemiology and potential causes, to its effect on patient lives and outcomes, as well as the basic science underpinning the unregulated cell growth that is the hallmark of the disease. Our Cancer podcasts illustrate the diversity of this research, and provide snapshots to the work of NDM scientists and clinicians to understand, treat and prevent cancer.

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Cancer

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