Deciphering the Dynamics of Epithelial-Mesenchymal Transition and Cancer Stem Cells in Tumor Progression

Abstract

The epithelial-mesenchymal transition (EMT) and the generation of cancer stem cells (CSCs) are two fundamental aspects contributing to tumor growth, acquisition of resistance to therapy, formation of metastases, and tumor relapse. Recent experimental data identifying the circuits regulating EMT and CSCs has driven the development of computational models capturing the dynamics of these circuits, and consequently various aspects of tumor progression. We review the contribution made by these models in (a) recapitulating experimentally observed behavior, (b) making experimentally testable predictions, and (c) driving emerging notions in the field, including the emphasis on the aggressive potential of hybrid epithelial-mesenchymal (E/M) phenotype(s). We discuss dynamical and statistical models at intracellular and population level relating to dynamics of EMT and CSCs, and those focusing on interconnections between these two processes. These models highlight the insights gained via mathematical modeling approaches and emphasizes that the connections between hybrid E/M phenotype(s) and stemness can be explained by analyzing underlying regulatory circuits. Such experimentally curated models have the potential of serving as platforms for better therapeutic design strategies.