Computation of the conditions for anti-angiogenesis and gene therapy synergistic effects: Sensitivity analysis and robustness of target solutions

Abdoulaye Diouf (1) , Houda Mokrani (2) , Evans Afenya (3) , Baba Issa Camara (4)

1 UASZ - Université Assane Seck de Ziguinchor [Sénégal]
2 LMRS - Laboratoire de Mathématiques Raphaël Salem
3 Elmhurst College
4 LIEC - Laboratoire Interdisciplinaire des Environnements Continentaux

Both anti-angiogenesis and gene therapy involve complex processes depending on non-point parameters belonging to a space of values. To successfully overcome the challenges involved in their therapeutic approaches, there is a need to analyze the sensitivity of these parameters. In this paper, a new mathematical model that combines immune system stimulations, inflammatory processes associated with tumor development, and gene therapy aimed at enhancing the efficacy of both treatments are explored. Using the global sensitivity methods of Sobol and Morris, the most important parameters are estimated. Estimation of the sensitivity variance revealed a strong interdependence between the parameters. Also, determinations of the conditions for effective therapy lead to a target of reducing the cancer cell numbers by at least 50 % . This opened the way for delimiting the parameter spaces making it possible to reach the treatment target in addition to enhancing the estimation of the minimum time of remission. The combination of therapies and sensitivity analysis have demonstrated the robustness of therapy success.

Mots clés: Cancer gene therapy; Oncolytic viruses; Inflammation; Mathematical model; isobologram analysis

Domaines: Planète et Univers [physics]

Abdoulaye Diouf, Houda Mokrani, Evans Afenya, Baba Issa Camara. Computation of the conditions for anti-angiogenesis and gene therapy synergistic effects: Sensitivity analysis and robustness of target solutions. Journal of Theoretical Biology, 2021, 528, pp.110850. ⟨10.1016/j.jtbi.2021.110850⟩. ⟨insu-03712676⟩