Tumour cell death and its fundamental role in establishing a pro-tumourigenic microenvironment (360G-Wellcome-313813_Z_24_Z)

From the earliest days of our training, biologists are taught that evasion of cell death is a hallmark of cancer. However, it appears that cell death also has a transformative effect on the tumour microenvironment, paradoxically fuelling tumour progression. Furthermore, the pro-tumourigenicity of cell death undercuts the treatment of cancer in the clinic. During my post-doctoral research, I developed advanced biosensors and novel techniques to comprehensively live-image cell death in Drosophila. Using this model, I discovered that macrophages exhibit unrestrained uptake of cellular debris, which can compromise their response to tissue damage. I also revealed that different types of cell death present distinct challenges to the macrophages tasked with clearing them. Here, I will interrogate the fundamental role of cell death during tumourigenesis. I will combine Drosophila’s genetics with in vivo live-imaging, laser-ablation, spatial transcriptomics and mammalian organoid co-culture in order to: 1) Define the contribution of different types of cell death and their clearance to tumourigenesis. 2) Determine how tumour cell death alters the behaviour of tumour-associated macrophages. 3) Interrogate therapy-induced tumour cell death and maximise its efficacy. Ultimately, my aim is to obtain a better fundamental understanding of tumour cell death and leverage this knowledge to improve treatment.