Epithelial/mesenchymal plasticity: how have quantitative mathematical models helped improve our understanding?

Area of Science:

• Oncology
• Cell Biology
• Mathematical Biology

Background:

• Phenotypic plasticity, the reversible alteration of cell phenotypes, poses a major challenge in solid tumor treatment.
• Tumor cells exploit this plasticity for therapy evasion, metastasis, and organ colonization, accelerating cancer progression.
• Bidirectional conversions between epithelial, mesenchymal, and hybrid epithelial/mesenchymal (E/M) phenotypes exemplify this plasticity.

Purpose of the Study:

• To explore the role of quantitative mathematical models in understanding phenotypic plasticity in cancer.
• To explain how these models elucidate molecular mechanisms driving E/M plasticity.
• To provide a conceptual framework for how signals influence E/M plasticity at single-cell and population levels.

Main Methods:

• Review and discussion of existing quantitative mathematical models of phenotypic plasticity.
• Analysis of how models explain experimental data and guide future research.
• Integration of single-cell and population-level perspectives on E/M plasticity.

Main Results:

• Mathematical models serve as hypothesis-generating tools for understanding cancer cell plasticity.
• These models help explain how intracellular and extracellular signals drive E/M transitions.
• The models offer insights into the heterogeneity and complexity of these cellular state changes.

Conclusions:

• Quantitative models are crucial for deciphering the mechanisms of phenotypic plasticity in solid tumors.
• Understanding E/M plasticity through modeling can reveal drivers of aggressive cancer phenotypes.
• This approach enhances our conceptual framework for tackling tumor progression and metastasis.