Preprint Article Version 1 This version is not peer-reviewed

Cancer Dynamics: Identification of States for Therapeutic Intervention

Version 1 : Received: 27 April 2020 / Approved: 5 May 2020 / Online: 5 May 2020 (05:55:27 CEST)

How to cite: Jangid, A.; Malik, M.Z.; Ramaswamy, R.; Singh, R.K.B. Cancer Dynamics: Identification of States for Therapeutic Intervention. Preprints 2020, 2020050063 (doi: 10.20944/preprints202005.0063.v1). Jangid, A.; Malik, M.Z.; Ramaswamy, R.; Singh, R.K.B. Cancer Dynamics: Identification of States for Therapeutic Intervention. Preprints 2020, 2020050063 (doi: 10.20944/preprints202005.0063.v1).

Abstract

We study a minimal model of the stress-driven p53 regulatory network that includes competition between active and mutant forms of the tumor-suppressor gene p53. Depending on the nature of the external stress signal, four distinct dynamical states are observed. These states can be distinguished by di erent dynamical properties and correspond to active, apoptotic, pre-malignant and cancer states. Transitions between any two of these states are found to be unidirectional and irreversible if the stress signal is either oscillatory or constant. When the signal decays exponentially, the apoptotic state vanishes, and for low stress the pre-malignant state is bounded by two critical points, allowing the system to transition reversibly from the active to the pre-malignant state. For signi cantly large stress, the range of the pre-malignant state expands and the system moves to the cancerous state which is a stable attractor. This suggests that identi fication of the pre-malignant state may be important both for therapeutic intervention as well as for drug discovery.

Subject Areas

p53-Mdm2; mutant p53; oncogene; stress; regulatory network; cancer dynamics

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