title: A mathematical model for cell cycle-specific cancer virotherapy.
abstract: Oncolytic viruses preferentially infect and replicate in cancerous cells, leading to elimination of tumour populations, while sparing most healthy cells. Here, we study the cell cycle-specific activity of viruses such as vesicular stomatitis virus (VSV). In spite of its capacity as a robust cytolytic agent, VSV cannot effectively attack certain tumour cell types during the quiescent, or resting, phase of the cell cycle. In an effort to understand the interplay between the time course of the cell cycle and the specificity of VSV, we develop a mathematical model for cycle-specific virus therapeutics. We incorporate the minimum biologically required time spent in the non-quiescent cell cycle phases using systems of differential equations with incorporated time delays. Through analysis and simulation of the model, we describe how varying the minimum cycling time and the parameters that govern viral dynamics affect the stability of the cancer-free equilibrium, which represents therapeutic success.
authors.affiliation: Department of Mathematics, Vanderbilt University, Nashville, TN 37240, USA. joseph.j.crivelli@vanderbilt.edu
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Crivelli
authors.forename: Juraj
authors.initials: J
authors.lastname: Földes
authors.forename: Peter S
authors.initials: PS
authors.lastname: Kim
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Wares
mesh_terms: D002453:Cell Cycle; D049109:Cell Proliferation; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology; D014779:Virus Replication