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. 2020 Jul 28;10:12652. doi: 10.1038/s41598-020-69380-6

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Critical irradiation doses and simulation trajectories for normal and cancer cells in response to combination therapies. (A) Critical irradiation doses for 6-day protocols after drip and oral inhibitor administration estimated in deterministic model simulations. Different bar colors correspond to different cycle durations, 12 (green), 18 (yellow), 24 (blue) and 36 h (red). Cells are irradiated at the beginning of each cycle, while the inhibitor is administrated at a day dose of 20 IC₅₀ at time points indicated by blue ovals (in the case of oral administration). (B,C,D) Deterministic simulation trajectories for normal, PTEN-cancer and Wip1-cancer cells in response to two irradiation doses, one above (red) and the other below (blue) IR_crit, for the protocol as in Fig. 2. The faded line segments visualize trajectories after the initiation of apoptosis.