Oncogenic signalling through transcriptional repression pathways in oesophageal adenocarcinoma.

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Cancer is a disease caused by the malfunction of "normal cells" in our bodies. This causes the cells to change their characteristics and begin to grow uncontrollably and move around the body. These changes to cellular characteristics are ultimately driven by molecular changes in our cells. Usually our cells contain pathways which act to maintain their normal functions. However, in cancer cells, mutational damage leads to hyperactivation of several pathways. It is unclear how these hyperactive pathways lead to cancer and this project aims to determine how this occurs in the context of oesophageal cancer. One pivotal event leading to changes in our cellular characteristics is the widespread changes that occur in the expression of our genes, both through changing the on or off state through regulatory proteins known as activators or repressors respectively. Ultimately, in cancer cells, many genes which are normally off are turned on and vice versa, leading to phenotypic changes that are characteristic of cancer such as increased growth or altered metabolism. Much focus has been placed on understanding how the gene on state is achieved, however in this project we will focus on the off state and how this is controlled in the context of cancer. We will focus on a particularly deadly form of cancer, oesophageal adenocarcinoma, and investigate how one commonly deregulated pathway (the ERBB2 pathway) controls this process. This is important as drugs which target the ERBB2 pathway are currently used to treat a range of cancers but resistance often arises. By identifying and providing mechanistic insight into additional downstream target molecules and pathways, we are likely to uncover potential new therapeutic opportunities.