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. Preprints2020, 2020050063. https://doi.org/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. https://doi.org/10.20944/preprints202005.0063.v1
Jangid, A.; Malik, M.Z.; Ramaswamy, R.; Singh, R.K.B. Cancer Dynamics: Identification of States for Therapeutic Intervention. Preprints2020, 2020050063. https://doi.org/10.20944/preprints202005.0063.v1
APA Style
Jangid, A., Malik, M.Z., Ramaswamy, R., & Singh, R.K.B. (2020). Cancer Dynamics: Identification of States for Therapeutic Intervention. Preprints. https://doi.org/10.20944/preprints202005.0063.v1
Chicago/Turabian Style
Jangid, A., Ram Ramaswamy and R. K. Brojen Singh. 2020 "Cancer Dynamics: Identification of States for Therapeutic Intervention" Preprints. https://doi.org/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.
Keywords
p53-Mdm2; mutant p53; oncogene; stress; regulatory network; cancer dynamics
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
