Engineering cancer dormancy as a collective emergent phenomenon: from matrix-enabled dormancy to collective dormancy-on-a-chip

Introduction

Cancer dormancy and the trigger to transition to active metastatic growth is a big open question. Current in vivo models focus on niche-specific cell and molecular mechanisms, ignoring biophysical aspects. Dormancy evolves with complex spatio-temporal dynamics; yet, there is a knowledge gap in the understanding of the heterogeneity of the units, and the dynamics of their interaction and evolution.

Emergence of Macro-Level Organization

Emergence occurs when a critical mass of units synergistically communicates, giving rise to a new macro-level organization, with properties greater than the sum of the units. Engineering emergent phenomena in biological systems is a big research challenge as they originate from multiscale communication.

DORMATRIX Proposal

In DORMATRIX, I propose a radically new view. I hypothesize that the balance between cancer dormancy and “awakening” is a collective emergent phenomenon, whereby a critical mass of micro-units communicates with each other and the environment in order to transition to metastatic growth.

Main Objective

The main objective of DORMATRIX is to engineer breast cancer (BC) dormancy as a collective emergent phenomenon using biomaterials-based dormancy-on-a-chip devices.

Previous Findings

My previous data shows that we can:

1. Apply biophysical cues to control BC proliferation.
2. Visualize in vivo early BC bone metastasis.

Multidisciplinary Approach

I will now address this outstanding challenge with a multidisciplinary approach:

1. Apply biophysical principles with novel biomaterials to model in vitro cancer micro-units.
2. Develop advanced 3D imaging to visualize collective cancer dormancy and bone microdamage.
3. Develop in silico models based on evolutionary game theory to predict the dynamics.
4. Prove my hypothesis with dormancy-on-a-chip devices.

Future Implications

Understanding the critical mass and multiscale communication required for emergent phenomena will enable the development of novel therapies to delay or prevent metastasis. The resulting technology for engineering emergent phenomena will spark research on other biological systems.