Quantitative modeling to understand cell signaling in the tumor microenvironment

https://doi.org/10.1016/j.coisb.2021.05.006Get rights and content
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Highlights

  • Complex signaling pathways in tumor, immune, and stromal cells in the tumor microenvironment drive tumor growth.

  • Mathematical models of signaling networks generate novel, actionable insight into cell behavior.

  • Models of intracellular signaling networks can be used to construct models of the multicellular tumor microenvironment.

Abstract

Tumor cells play a central role in multiple processes associated with cancer progression. They continuously interact with surrounding cells and the extracellular matrix, displaying various behaviors collectively known as hallmarks of cancer. Considering the complexity of the interactions between cells in the tumor microenvironment (TME), mathematical models of intracellular signaling within the multicellular environment in tumors are useful. In this review, we first give an overview of the TME, motivating the need for mathematical modeling, followed by a presentation of salient models of signaling in tumor cells, immune cells, and stromal cells. We posit that these published models provide exactly the foundation needed to build more comprehensive models that represent the multicellular TME and its rich network of intercellular interactions.

Keywords

Mechanistic model
Mathematical oncology
Tumor–immune interactions
Cell–cell interactions
Tumor stroma

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Authors contributed equally to this work.