Imaging Metallomics - Picturing Metal Behaviour in Cancer

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Metal ions have unique chemical properties that make some of them essential nutrients for human health. On the other hand, if their trafficking is dysregulated this can contribute to development of disease. Many drugs either (i) contain a metal in their structure or (ii) exert their action by influencing metal trafficking in our body. Drugs based on the metal platinum are widely used in the treatment of several cancers, including ovarian cancer, but unfortunately in many patients the tumour eventually stops responding to treatment and becomes 'platinum resistant', leaving patients with fewer therapeutic options and poorer survival rate. It has been found, from studies in cells and patient biopsies, that platinum resistant cancer tends to take up less of the platinum drug. While the exact mechanism through which platinum drugs enter the tumours is not fully known, some studies showed that these drugs could use the same 'doorway' into the cell used by copper, a metal essential for our health. Therefore, accumulation of platinum drugs in ovarian cancer, and potentially their ability to respond to these drugs, could be linked to the tumour's ability to accumulate copper. In this project, I will study the relationship between resistance to platinum drugs in ovarian cancer and its ability to accumulate these drugs and copper. I will also investigate whether removing copper, thus making the tumour more 'hungry' for this essential nutrient, will also trick it into taking up more platinum drugs, potentially reversing platinum resistance. To study all of this while it's happening inside the body, I will label both the platinum drugs and copper with a radioactive tag so that we can track them inside a living organism in real-time images using a scanner. This project will not only improve our understanding of why ovarian cancer becomes resistant to platinum drugs but will also enable the development of imaging-based tools to check if a patient's tumour is resistant to platinum drugs, so that the patient can be moved to different treatments. Finally, research into strategies to reverse platinum resistance will help increasing the number of patients that can benefit from platinum drugs.