Manipulating the hypoxic tumour microenvironment to study therapy resistance

This research focused on Notch and hypoxia and their interaction in cancer. The current knowledge of the role of Notch in breast cancer is reviewed as well as its role in the development, progression and resistance to therapy. Next was investigated the effect of hypoxia on Notch signalling in lung cancer and it was found that hypoxia is able to increase Notch signalling in cells. In the next chapters, a system was created to fluorescently label hypoxic cells to investigate their behaviour in tumours. This system was characterized and used it in a lung cancer model and it was shown that hypoxic cells can be tracked at single cells resolution in tumours. The research continues by including a way to kill labelled hypoxic cells in the system and using it in a breast cancer model to study the role of hypoxic cells in resistance to therapy. The research also made a new mouse model with the system to study hypoxic cells in spontaneous tumours.