Testing novel leukaemia treatments
University of Glasgow – Dr Helen Wheadon
According to figures from the Home Office and Cancer Research UK, approximately 23,000 mice are used per year to investigate leukaemia. This project aims to assess the utility of induced pluripotent stem cells (iPSCs) as a relevant model system for the pre-clinical testing of novel therapies to target cancer stem cells, especially in leukaemia. Currently, scientists rely on animals, such as mice, for the early or preclinical development of novel therapies in cancer.
Patient-derived induced pluripotent stem cells (iPSCs) provide a means of modelling cancer, especially diseases involving stem cells. Stem cells occur naturally in the body and function to sustain many of our tissues such as skin, liver, digestive system, nervous system and the blood. Stem cells have both the potential to develop into more mature functional cell types or to remain as stem cells by replicating themselves. Similar cells have been found in various cancers such as leukaemia, breast cancer, brain tumours and are termed cancer stem cells. They are resistant to treatment and survive despite the best current therapies, often causing the cancer to re-grow after treatment.
This project aims to assess the utility of iPSCs as a relevant model system for the pre-clinical testing of novel therapies to target cancer stem cells, which can lead to persistent, minimal, residual disease and relapse of leukaemia. At the present time, academic and commercial organisations rely heavily on animal models for the early or preclinical development of novel therapies, including “small molecule inhibitors” in cancer. Large numbers of these novel small molecules, which target specific abnormalities, are being generated, however very few make it to the clinic despite extensive experimentation on animals. According to figures from the Home Office and Cancer Research UK, approximately 23,000 mice are used per year to investigate leukaemia. These experiments include initial toxicity studies followed by testing the new treatment regimes using xenotransplantation, retroviral insertion of oncogenes or genetic mouse models to induce leukaemia. Many of these models involve irradiating the mice to eradicate the blood system prior to transplantation with leukaemic cells. On developing leukaemia, the mice are monitored prior to being sacrificed. Although the experiments are deemed to be of moderate severity, mice often develop other signs of distress/sickness including weight loss, fur ruffling, back hunching, diarrhoea as well as increased white blood cell counts.