Investigating the influence of growth arrest mechanisms on tumour responses to radiotherapy

by Chole Colson, Philip K Maini & Helen M Byrne

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In this paper, we investigate how nutrient and space limited mechanisms of growth control impact tumour responses to radiotherapy (RT). By distinguishing three growth regimes: nutrient limited (NL), space limited (SL) and bistable (BS), where both mechanisms of growth arrest are active, our study reveals qualitative differences between the RT responses of tumours in the monostable (i.e., NL and SL) regimes and the BS regime. In particular, NL and SL tumours have largely positive responses to treatment, while RT is deleterious for tumours in the BS regime. We find that the positive and negative responses observed in the monostable and BS regimes, respectively, may be underpinned by different biological mechanisms. Further, the RT dosing strategies that maximise the reduction in tumour burden also vary between regimes; higher doses applied at higher frequencies are beneficial for SL tumours, whereas lower doses applied at lower frequencies can prove more effective for NL and BS tumours. Subject to validating our findings against experimental data, we believe that our modelling framework may help guide patient-specific treatment protocol design and, thus, contribute to improving patient prognosis.

Chloé Colson is a PhD student, Philip K. Maini is a Professor of Mathematical Biology and director of the Wolfson Centre for Mathematical Biology, and Helen M. Byrne is a Professor of Mathematical Biology.