Scheme: Wolfson Research Merit Awards
Organisation: Institute of Cancer Research
Dates: Apr 2012-Mar 2017
Summary: A key problem in the treatment of breast cancer is the acquired resistance of the cancer cells to bypass the cell death programmes. It is now clear that cell death acts as part of a quality-control and repair mechanism that eliminates potentially harmful cells, and failure to do so is linked to cancer. Therefore, a better understanding of the molecular processes regulating cell death and cell survival will provide the basis for more rational cancer therapies in the future. Our observations inform us about the genes that are involved in cancer and the basic biology of the complex relationship between inflammation and cell death. This fundamental knowledge is key for the development of better predictions for therapy response and more effective targeted treatments for people with breast cancer. Moreover, despite decades of successful use of cytotoxic chemotherapy in cancer, the biological basis for its differential success among individuals and for the existence of a therapeutic index has remained largely obscure. We propose that individual variation in clinical behaviour, and the adaptive nature of tumours, rely on a common principle in which cancer-related inflammation facilitates tissue-remodelling, adaptation to tissue stress and drug resistance. The principle idea addressed by my lab is that cell survival and adaptation mechanisms of tumours are supported, at least in part, by cancer-related inflammation, and that this can be successfully targeted by switching the inflammatory response to cell death, causing tumours to permanently regress.