Evolution of the Supermodel: Progress in Modelling Radiotherapy Response in Mice

Abstract

Mouse models are essential tools in cancer research that have been used to understand the genetic basis of tumorigenesis, cancer progression and to test the efficacies of anticancer treatments including radiotherapy. They have played a critical role in our understanding of radiotherapy response in tumours and normal tissues and continue to evolve to better recapitulate the underlying biology of humans. In addition, recent developments in small animal irradiators have significantly improved in vivo irradiation techniques, allowing previously unimaginable experimental approaches to be explored in the laboratory. The combination of contemporary mouse models with small animal irradiators represents a major step forward for the radiobiology field in being able to much more accurately replicate clinical exposure scenarios. As radiobiology studies become ever more sophisticated in reflecting developments in the clinic, it is increasingly important to understand the basis and potential limitations of extrapolating data from mice to humans. This review provides an overview of mouse models and small animal radiotherapy platforms currently being used as advanced radiobiological research tools towards improving the translational power of preclinical studies.

Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

“…Mice have been used in many biological studies ranging from pharmacology, drug development, and as disease models [118]. Radiation oncology has also benefitted from pre-clinical studies using the large variety of genetically modified mouse models [119,120]. Using conventionally accelerated protons or external beam radiotherapy for in vivo experiments is however much easier than doing similar experiments with laser-driven proton beams since, as mentioned earlier, the beam energy attained with laser-driven protons is generally not yet sufficient to fully irradiate deep-seated tumours with the required doses.…”

Cardiac sub-volume targeting demonstrates regional radiosensitivity in the mouse heart

“…Whilst acknowledging the potential challenges of modelling radiation therapy response in mice [17] we have, for the first time, directly recapitulated clinical observations highlighting the base of the heart as a radiosensitive substructure. In our model, radiation dose to the base of the heart leads to systolic dysfunction manifested as decreased FS and EF compared to nonirradiated age-matched controls.…”

Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer

“…This paradigm was proven in mice; for example, a study demonstrating that three fractions of eight Gy had a better response than five fractions of six Gy in inducing anti-tumor immunity in combination with anti-CTLA-4 antibodies [ 33 ]. However, the physical and immunological impacts of XRT for mice and humans are not the same [ 34 ], making it difficult to relay on pre-clinical evidence for choosing the optimal manner to treat people. Some data from human studies besides our own also contradict the mice data.…”