"Challenges in silico: modelling delays, death and repair in EMT6/Ro tumor cells under a variety of multi-dose irradiation protocols"

Abstract: In silico (computational) techniques offer the potential to investigate efficiently many aspects of tumour development and progression. In particular, a calibrated, dynamic, in silico tumour model could be used to probe the combinatorially extensive, and largely unexplored, irradiation protocol space (dose size and timing sequence) in a facile way, with the potential to discover large gains in efficacy within a given total dose envelope, meriting further clinical investigation. However, to do this, the tumour model must present realistic delay, death and repair dynamics under multi-dose irradiation. Given that the exact mechanism of repair, cell cycle delay and death is not perfectly understood, the calibration approach itself allows for the testing of various theoretical assumptions. Our study, building on our previous work with single-dose irradiation (Angus & Piotrowska, 2013), finds that delay--death--repair dynamics are well represented by a reciprocal repair function (Fowler, 1999 & 2002) which includes an unrepairable cell fraction (Carabe-Fernandez, 2001).