Modeling of Tumor Growth with Input from Patient-Specific Metabolomic Data

Abstract

Advances in omic technologies have provided insight into cancer progression and treatment response. However, the nonlinear characteristics of cancer growth present a challenge to bridge from the molecular- to the tissue-scale, as tumor behavior cannot be encapsulated by the sum of the individual molecular details gleaned experimentally. Mathematical modeling and computational simulation have been traditionally employed to facilitate analysis of nonlinear systems. In this study, for the first time tumor metabolomic data are linked via mathematical modeling to the tumor tissue-scale behavior, showing the capability to mechanistically simulate cancer progression personalized to omic information obtainable from patient tumor core biopsy analysis. Generally, a higher degree of metabolic dysregulation has been correlated with more aggressive tumor behavior. Accordingly, key parameters influenced by metabolomic data in this model include tumor proliferation, vascularization, aggressiveness, lactic acid production, monocyte infiltration and macrophage polarization, and drug effect. The model enables evaluating interactions of interest between these parameters which drive tumor growth based on the metabolomic data. The results show that the model can group patients consistently with the clinically observed outcomes of response/non-response to chemotherapy. This modeling approach provides a first step towards evaluation of tumor growth based on tumor-specific metabolomic data.

Keywords: Cancer; Computational simulation; Mathematical modeling; Metabolomics; Personalized medicine.