Tumour suppressor mediated mechanisms of angiogenesis inhibition

In order for tumours to become large and life threatening they must first develop a network of blood vessels in order to deliver oxygen and nutrients to cancer cells. The process of blood vessel formation, called angiogenesis, is an absolutely necessary step in the formation of solid tumours and an ideal point at which novel therapeutic agents can be developed. Our previous work demonstrated that the natural mechanisms of the human body that prevent cancer do so by inhibiting angiogenesis. We showed that the p53 tumour suppressor, which is mutated in half of all human cancers, stimulates the production of a natural anti-angiogenic factor called Arresten. When p53 becomes mutated in tumours, levels of Arresten are decreased and cancer growth accelerates. In this current application we propose to study the levels of Arresten circulating in the bloodstream of patients with ovarian, breast and prostate cancer. It is our hope that the development of this form of test can provide a new and powerful tool for the diagnosis of these cancers and possibly indicate when events such as metastasis have occurred. In addition, we will study the biochemical pathways in human cells by which Arresten is produced in the hopes of learning how production of such factors can be enhanced in the fight against cancer.