From compost bin to the clinic: what can fruit flies teach us about treating cancer with radiotherapy?

Radiotherapy is a powerful tool in oncology, from curative treatments to palliative care. However, the efficacy of radiotherapy is limited by side effects caused by damage to healthy tissues. Ultrahigh dose-rate radiotherapy (UHDR-RT) has emerged as a possible method of reducing damage to normal tissues while maintaining the ability to control the progression of cancer. UHDR treatments are delivered three orders of magnitude faster than conventional treatments. To reach the dose rates associated with UHDR-RT, novel radiation sources have been developed, spanning a wide range of radiation types, energies, and time structures of delivery. These include kilovoltage x-rays produced by a shutter-controlled x-ray tube, and very high energy electrons (VHEE) accelerated to 200 MeV at the CERN Linear Electron Accelerator for Research (CLEAR). Testing the capability of these sources requires radiobiological models which are not commonly used in modern radiotherapy. Drosophila melanogaster became integral to understanding the biological effects of radiation with Hermann J. Muller's Nobel winning discovery of x-ray induced mutagenesis in the 1920s. Nearly a century later, Drosophila are a valuable tool in advancing our understanding of the effects of UHDR radiation and how we can translate research into better care for radiation oncology patients.