PT  - JOURNAL ARTICLE
AU  - Marta Leocata
AU  - J. C. L. Alfonso
AU  - Nikos I. Kavallaris
AU  - Haralampos Hatzikirou
TI  - A novel averaging principle provides insights in the impact of intratumoral heterogeneity on tumor progression
AID  - 10.1101/584490
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 584490
4099  - http://biorxiv.org/content/early/2019/03/25/584490.short
4100  - http://biorxiv.org/content/early/2019/03/25/584490.full
AB  - Typically stochastic differential equations (SDEs) involve an additive or multiplicative noise term. Here, we are interested in stochastic differential equations for which the white noise is non-linearly integrated in the corresponding evolution term, typically termed as random ordinary differential equations (RODEs). The classical averaging methods fail to treat such RODEs. Therefore, we introduce a novel averaging method appropriate to be applied on RODEs. To exemplify the importance of our method, we apply it in an important biomedical problem, i.e. the assessment of intratumoral heterogeneity impact on tumor dynamics. In particular, we model gliomas according to a well-known Go or Grow (GoG) model and tumor heterogeneity is modelled as a stochastic process. It has been shown that this GoG model exhibits an emerging Allee effect (bistability). We analytically and computationally show that the introduction of white noise, as a model of intratumoral heterogeneity, leads to a monostable tumor growth. This monostability behaviour is also derived even when spatial cell diffusion is taking into account.