A novel averaging principle provides insights in the impact of intratumoral heterogeneity on tumor progression

Haralampos Hatzikirou, Nikos I. Kavallaris, Marta Leocata

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 nonlinearly integrated into 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 to a specific class of RODEs. To exemplify the importance of our method, we apply it to an important biomedical problem, in particular, we implement the method to the assessment of intratumoral heterogeneity impact on tumor dynamics. Precisely, we model gliomas according to a well-known Go or Grow (GoG) model, and tumor heterogeneity is modeled as a stochastic process. It has been shown that the corresponding deterministic GoG model exhibits an emerging Allee effect (bistability). In contrast, we analytically and computationally show that the introduction of white noise, as a model of intratumoral heterogeneity, leads to monostable tumor growth. This monostability behavior is also derived even when spatial cell diffusion is taken into account.

Original languageBritish English
Article number2530
JournalMathematics
Volume9
Issue number20
DOIs
StatePublished - 1 Oct 2021

Keywords

  • Averaging
  • Intrinsic heterogeneity
  • Phenotypic switching
  • Tumor growth
  • White noise

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