title: Combined therapies of antithrombotics and antioxidants delay in silico brain tumour progression.
abstract: Glioblastoma multiforme (GBM), the most frequent type of primary brain tumour, is a rapidly evolving and spatially heterogeneous high-grade astrocytoma that presents areas of necrosis, hypercellularity and microvascular hyperplasia. The aberrant vasculature leads to hypoxic areas and results in an increase in oxidative stress, selecting for more invasive tumour cell phenotypes. In our study, we assay in silico different therapeutic approaches which combine antithrombotics (ATs), antioxidants and standard radiotherapy (RT). To do so, we have developed a biocomputational model of GBM that incorporates the spatio-temporal interplay among two glioma cell phenotypes corresponding to oxygenated and hypoxic cells, a necrotic core and the local vasculature whose response evolves with tumour progression. Our numerical simulations predict that suitable combinations of ATs and antioxidants may diminish, in a synergistic way, oxidative stress and the subsequent hypoxic response. This novel therapeutical strategy, with potentially low or no toxicity, might reduce tumour invasion and further sensitize GBM to conventional RT or other cytotoxic agents, hopefully increasing median patient overall survival time.
authors.affiliation: Departamento de Matemáticas, Universidad de Castilla-La Mancha, ETSI Industriales, Avda. Camilo José Cela 3, 13071 Ciudad Real, Spain alicia.martinez@uclm.es.
authors.forename: Alicia
authors.initials: A
authors.lastname: Martínez-González
authors.affiliation: Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Durán-Prado
authors.affiliation: Departamento de Matemáticas, Universidad de Castilla-La Mancha, ETSI Caminos, Canales y Puertos, Avda. Camilo José Cela 3, 13071 Ciudad Real, Spain.
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Calvo
authors.affiliation: Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alcaín
authors.affiliation: Servicio de Oncología Radioterápica, Hospital General Universitario de Salamanca, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Romasanta
authors.affiliation: Departamento de Matemáticas, Universidad de Castilla-La Mancha, ETSI Industriales, Avda. Camilo José Cela 3, 13071 Ciudad Real, Spain.
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Pérez-García
mesh_terms: D000975:Antioxidants; D003131:Combined Modality Therapy; D003198:Computer Simulation; D005343:Fibrinolytic Agents; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008962:Models, Theoretical; D011878:Radiotherapy
chemical_list: D000975:Antioxidants; D005343:Fibrinolytic Agents
keywords: antioxidants; antithrombotic; combined therapies; glioblastoma multiforme; radiotherapy