A Kinetic Modeling for Radiotherapy Mechanisms with Gene-Environment Network (GEN) Framework

Radiotherapy is a comprehensive method, in which the main factor that determines success in clinical radiotherapy is radiation dose. It is necessary to make the most of mathematical theories to investigate the complicated mechanisms how P53-dependent regulation pathways govern cell survival and apoptosis at molecular level. In this work, we develop an integrated method for modeling Tumor Radiotherapy System (TRS) based on Kinetic Theory of Active Particle (KTAP) and Gene-Environment Network (GEN), and then explore the dynamics of integrated TRS through correlated subsystems, and inner mechanism of cell fate decision under radiotherapy. The inner mechanisms of radiotherapy are investigated at both molecular and systematic levels, including the stochastic kinetics of DNA damage generation and repair, switch-like Ataxia Telangiectasia Mutated (ATM) activation, oscillation of P53-Mouse Mouble Minute 2 homolog (MDM2) negative feedback loop, and outcome of tumor cell degradation and genome stability under radiotherapy.

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