A Computational Framework to Assess the Efficacy of Cytotoxic Molecules and Vascular Disrupting Agents against Solid Tumours

¹ UJF-Grenoble 1, CNRS, Laboratory TIMC-IMAG UMR 5525 DyCTiM research team, 38041 Grenoble, France
² INSERM U836, Grenoble Institut des Neurosciences, UJF-Grenoble 1 CHU Michallon, 38042 Grenoble, France
³ Ecrins therapeutics, BIOPOLIS, 38700 La Tronche, France

^⋆ Corresponding author. E-mail: Angelique.Stephanou@imag.fr

Abstract

A computational framework for testing the effects of cytotoxic molecules, specific to a given phase of the cell cycle, and vascular disrupting agents (VDAs) is presented. The model is based on a cellular automaton to describe tumour cell states transitions from proliferation to death. It is coupled with a model describing the tumour vasculature and its adaptation to the blood rheological constraints when alterations are induced by VDAs treatment. Several therapeutic protocols in two structurally different vascular networks were tested by varying the duration of cytotoxic drug perfusion and the periodicity of treatment cycles. The impact of VDAs were also tested both experimentally from intravital microscopy through a dorsal skinfold chamber on a mouse and numerically. Simulation results show that combining cytotoxic treatment with a post treatment of VDA through a judicious timing could favour the rapid eradication of the tumour. The computational framework thus gives some insights into the outcome of cytotoxic and VDAs treatments on a qualitative basis. Future validation from our experimental setup could open up new perspectives towards Computer-Assisted Therapeutic Strategies.