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A quantitative study on the role of TKI combined with Wnt/β-catenin signaling and IFN-α in the treatment of CML through deterministic and stochastic approaches

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  • Pan, Sonjoy
  • Raha, Soumyendu
  • Chakrabarty, Siddhartha P.

Abstract

We propose deterministic and stochastic models for studying the pharmacokinetics of chronic myeloid leukemia (CML), in the presence of CTL immune response, upon administration of IFN-α (the traditional treatment for CML), TKI (the current frontline medication for CML) and Wnt/β-catenin signaling (the state-of-the art therapeutic breakthrough for CML). To the best of our knowledge, no mathematical model incorporating all these three therapeutic protocols are available in literature. The stability analysis of the system equilibria is undertaken in terms of a threshold parameter. Further, this work introduces a stochastic approach in the study of CML dynamics. The evolution of the dynamics for both the deterministic and the stochastic models are examined. This study addresses the question of how the dual therapy of TKI and Wnt/β-catenin signaling or triple combination of all three, offers potentially improved therapeutic responses, particularly in terms of reducing side effects of TKI or IFN-α. The probability of CML extinction/remission based on the level of CML stem cells at detection is also predicted.

Suggested Citation

  • Pan, Sonjoy & Raha, Soumyendu & Chakrabarty, Siddhartha P., 2020. "A quantitative study on the role of TKI combined with Wnt/β-catenin signaling and IFN-α in the treatment of CML through deterministic and stochastic approaches," Chaos, Solitons & Fractals, Elsevier, vol. 133(C).
    • Handle: RePEc:eee:chsofr:v:133:y:2020:i:c:s0960077920300266
    DOI: 10.1016/j.chaos.2020.109627
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    References listed on IDEAS

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    1. Svetlana Bunimovich-Mendrazitsky & Benzion Shklyar, 2017. "Optimization of Combined Leukemia Therapy by Finite-Dimensional Optimal Control Modeling," Journal of Optimization Theory and Applications, Springer, vol. 175(1), pages 218-235, October.
    2. Marieke A. G. Essers & Sandra Offner & William E. Blanco-Bose & Zoe Waibler & Ulrich Kalinke & Michel A. Duchosal & Andreas Trumpp, 2009. "IFNα activates dormant haematopoietic stem cells in vivo," Nature, Nature, vol. 458(7240), pages 904-908, April.
    3. Rădulescu, I.R. & Cândea, D. & Halanay, A., 2016. "Optimal control analysis of a leukemia model under imatinib treatment," Mathematics and Computers in Simulation (MATCOM), Elsevier, vol. 121(C), pages 1-11.
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    1. Svetlana Bunimovich-Mendrazitsky & Benzion Shklyar, 2017. "Optimization of Combined Leukemia Therapy by Finite-Dimensional Optimal Control Modeling," Journal of Optimization Theory and Applications, Springer, vol. 175(1), pages 218-235, October.

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