Microenvironment-mediated cancer dormancy: Insights from metastability theory

Area of Science:

• Biophysics
• Cancer Biology
• Cellular Dynamics

Background:

• Dormancy is a conserved survival mechanism, notably seen in cancer metastasis where cells arrest growth for extended periods.
• The tumor microenvironment significantly influences cancer cell dormancy, with increasing focus on molecular and signaling pathways.
• Both intracellular and extracellular biochemical and mechanical cues are implicated in regulating dormant states.

Purpose of the Study:

• To provide a physical perspective on cancer dormancy and tumor growth, independent of specific molecular details.
• To classify proposed dormancy mechanisms using thermodynamic metastability concepts.
• To associate local energy minima in tissue growth kinetics with dormant states.

Main Methods:

• Analogies between tissues and fluids.
• Application of thermodynamic phase separation concepts.
• Classification of mechanisms based on thermodynamic metastability.
• Drawing parallels with clinical and experimental data.

Main Results:

• Proposed a framework classifying dormancy mechanisms via thermodynamic metastability.
• Linked microenvironment interactions (adherence, mechanical confinement) to metastability.
• Associated local energy minima in tissue growth kinetics with dormant states.

Conclusions:

• A physical, thermodynamic framework can globally describe cancer dormancy and tumor growth.
• Metastable states, influenced by the microenvironment, are key to understanding dormancy.
• This approach offers a simplified yet comprehensive view of complex cancer cell behaviors.