Grant: Operating Grant

We have previously discovered that cancer causing genes (oncogenes) are responsible for the ability of tumor cells to attract blood vessels (angiogenesis), which they need to grow and spread (progression). Recently we have identified a completely new mechanism that may facilitate such communication between cancer cells and blood vessels. Thus, cancer cells containing active oncogenes produce myriads of tiny bubbles (vesicles, microvesicles or oncosomes), which contain the oncogenic proteins themselves, and can transfer them from cell to cell, causing angiogenesis and cancer progression. We have preliminary data to suggest that oncosomes can also be easily collected from blood of cancer patients, and their content decoded to inform us how to treat the tumour (what oncogenes are present) and whether the treatment actually works in a given patient. It is essential that we understand exactly how this works: How do cancer causing oncogenes trigger cellular bubbling (oncosome formation), and how different are oncosomes from bubbles produced by some agitated normal cells (e.g. blood vessel cells). None of this is known, especially whether oncosomes mainly come from within the cancer cell (exosomes) or from the cellular surface (ectosomes), or both/neither. We will examine the molecules that control these processes, and how their actions are altered in cancer cells (neovesiculation). Knowing this would allow us to devise drugs that block formation of oncosomes, or inhibit their interactions with blood vessels. We already found one (Diannexin). We will use advanced technology to study active molecules present within oncosomes and we will assess how they change when tumors are treated with various drugs. We will use this information to explore ways to block cancer-promoting effects of oncosomes. This knowledge will also serve to develop a new oncosome-based blood test, to follow and modulate anticancer treatments and improve their results.