Chemical bioreductive approaches to targeted radiosensitisation and imaging of tumours

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All cells in the human body require oxygen to survive. The condition where insufficient oxygen is available, as occurs in heart attacks and strokes for example, is referred to as hypoxia.The human body is designed to resist the formation of tumours, so any developing tumour faces many challenges, one of which is oxygen supply. Unfortunately, tumours manage to overcome this challenge and cheat the body into providing oxygen to a greater or lesser extent.The tumour cells, which receive insufficient oxygen and experience hypoxia, adapt to this condition and in so doing become stronger and more difficult to kill.In particular, hypoxic tumour cells are more resistant to radiotherapy than tumour cells that receive sufficient oxygen.Clearly, as 50% off all people treated for cancer receive radiotherapy, it is important to find ways of making this treatment more effective against hypoxic tumour cells. Presently, the more hypoxic the cancer the less effective is the radiotherapy treatment.This new work is a collaboration between the Chemistry Department and Oncology at Oxford who together have come up with a way to tackle hypoxic tumour cells.So far, the chemists have made a drug, which can kill hypoxic tumour cells and make them more susceptible to radiotherapy, but does not harm normal cells. The biologists have tested this drug on hypoxic human cancer cells grown in the laboratoryAs a next step, we would like to be able to make more of this new drug and to test it further both in the laboratory and in mice. This kind of testing is essential if this drug is ever going to progress to being useful in combination with radiotherapy for cancer patients. We also plan to modify the drug so that it becomes fluorescent as soon as it becomes active in hypoxic conditions. This will make the biological testing much easier as we will be able to see exactly when and where it becomes active.In summary, the more hypoxic a tumour is the more likely it is to kill the patient. Therefore, our approach to target these cells specifically could have a major impact on patient survival.