Radiotherapy is a central component in cancer treatment due to its contribution to cures (40%) and its cost effectiveness. Its efficacy is hampered by the toxicity of radiation and the radio resistance of certain tumours. To overcome these limitations, we need to identify factors of tumour radio-resistance and organismal sensitivity, with the aim of developing treatments that combine radiotherapy with drugs that specifically radio sensitise tumour cells or protect the healthy tissue. This is an active area of research that has been become a priority in cancer research in the UK.
Before progress reaches the translational stage, in vivo evidence is essential in this field, and comes mostly from work on mice and rats. We aim at establishing Drosophila as an in vivo model for radiation research, to serve as replacement for rodents. We will focus on the intestine, as this organ is highly similar in flies and mammals and it is of high medical relevance in cancer radiotherapy.
To establish the fly intestine as an in vivo model for radiation resistance and tolerance, we need to show that it mimics the basic phenomenology that we want to study. To do that, we will test whether:
(1) the fly displays intestinal malfunction (absorption, epithelial barrier) after irradiation,
(2) different cell types have differential sensitivity to radiation (as is the case in mammals) and the tissue engages in a regenerative response,
(3) we can observe cytoprotective effects after irradiation by either overexpressing in the fly gut factors known to enhance radiation tolerance or feeding flies with a radio-protective drug, and
(4) we can observe, in fly intestines that are genetically mosaic for factors known to confer radiation tolerance in tumours, differential radio-resistance between the mutant and wild type tissue. Establishing these observations would support our proposal that the fly intestine is a good in vivo model for radiation research that can replace the use of rodents.