Abstract
<title>Abstract</title> <p>We present a theoretical–oncology framework in which cancer initiation and therapy response are governed by a bistable order–repair transition. Our principal innovation is to couple evolutionary (sensitive/resistant) therapy dynamics to a single bistable order parameter I representing multicellular information integrity: healthy tissue is a directionally ordered, cooperative medium eroded by a state-dependent stress flux and restored by repair such that the mean-field reduction dI/dτ = µ(I)(1 − I) − ρI possesses a low-order attractor identified with the atavistic (quasinunicellular) phenotype. Across a paired cohort of n = 500 virtual mice, survival under DNA-damaging protocols increases monotonically from the maximum tolerated dose toward evolutionary-steering plus suppression of stress-induced mutagenesis (A2 + A3 Adaptive + SIM-block: median 168 d vs 74 d for MTD), whereas only protocols targeting recently evolved vulnerabilities—adaptive immunity and redifferentiation—yield long-term survivors (A1 + A4 Immuno + Diff: 33% survival on day 400). A Latin-hypercube global sensitivity analysis (± 30% on nine parameters) revealed that the drug-arm ordering was preserved in 100% of the samples and that the young-target survival advantage was 94%. The model provides a single dynamical framework consistent with the therapeutic corollary of the atavism hypothesis — target the weakness, not the strength — deriving it from dynamical structure rather than tuned assumptions. It is hypothesis-generating rather than confirmatory.</p>