Bullock - Fellowship - Characterisation of deregulated ...

Bowel cancer is the second most common cause of death from cancer in Europe. The vast majority of deaths are not however caused by the cancer itself (which is often treatable with surgery), but by metastasis (cancer spread), to which the most troublesome symptoms can be attributed and to which most patients eventually succumb. Metastasis is a complex multi-step process about which very little is understood. Unfortunately, this lack of detailed knowledge acts as a barrier to the development of drugs capable of treating or preventing cancer spread. In addition, current treatment methods generally produce disappointing results, highlighting the need for further research in this field. Some interesting discoveries have recently been made. For example; studies have shown that bowel cancers spread with the help of various cells that exist in the tissues surrounding them. Interaction between these cells appears to influence how aggressively cancer spreads and although many questions remain to be answered, developing a better understanding of this interplay may uncover new opportunities for drug development. MicroRNAs are a recently discovered form of genetic material. They are expressed in healthy tissue, but corrupted in cancer. They control numerous genes and influence processes involved in metastasis formation and are potential drug targets. However, no previous studies have scrutinised their presence in tissue surrounding bowel cancer, nor do we understand how microRNAs in the surrounding tissue affect cancer spread. I am a 3rd year surgical trainee with a deep curiosity about the fundamental causes of bowel cancer. I am currently studying for a PhD in cancer science in collaboration with a group of highly experienced, highly reputed surgeons, scientists and pathologists. The aim of my project is to study the role of microRNAs in bowel cancer spread by examining human bowel cancer specimens and the tissues surrounding them. I have compared microRNAs in samples from patients who died from cancer spread with those who never developed metastases and have a list of microRNAs that I feel are likely to play an important role. The mechanisms by which abnormal microRNA expression influences bowel cancer spread will be explored using tried and tested laboratory techniques which enable us to quantify cancer invasion and metastasis development. I have also developed a novel artificial cancer model called an organotypic, in which colon cancer cells are grown on a synthetic scaffold containing cells found in the tissue surrounding cancers. This model has already enabled me to demonstrate in a persuasive and visually compelling way, how certain microRNAs enhance invasion and promote colon cancer spread. As a collaborative group, we offer a unique blend of expertise and provide an excellent platform on which to base this project. A surgical perspective is particularly valuable, as it ensures that our research focus remains concentrated in areas of genuine clinical need and that novel laboratory findings can be rapidly transposed to the clinical setting.