Glioblastoma multiforme, the most frequent type of primary brain tumor, 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 of the
oxidative stress selecting for more invasive tumor cell phenotypes. In our
study we assay in silico different therapeutic approaches which combine
antithrombotics, antioxidants and standard radiotherapy. To do so, we have
developed a biocomputational model of glioblastoma multiforme 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 tumor progression. Our numerical simulations predict that
suitable combinations of antithrombotics and antioxidants may diminish, in a
synergetic way, oxidative stress and the subsequent hypoxic response. This
novel therapeutical strategy, with potentially low or no toxicity, might reduce
tumor invasion and further sensitize glioblastoma multiforme to conventional
radiotherapy or other cytotoxic agents, hopefully increasing median patient
overall survival time.Comment: 8 figure