Human Cancer Genetics

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.

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.

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.

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.

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 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.

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.

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.

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.

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.