Project description
Engineering cancer dormancy on a chip
Advances in targeted therapies and immunotherapies have generated optimism about cancer treatment. However, not all patients respond successfully: drug resistance frequently occurs, and many relapse due to dormant cancer cells. It remains unclear what reactivates dormant cancer cells and causes them to metastasise from their original site. The ERC-funded DORMATRIX project will work on a revolutionary idea that the awakening of cancer cells from dormancy is driven by complex dynamics and communication with the environment. Researchers plan to recreate breast cancer dormancy in tumour-on-a-chip devices. Advance 3D imaging and in silico models will help predict dormancy dynamics, paving the way for therapies that delay or prevent metastasis.
Objective
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 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.
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. 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.
My previous data shows that we can (i) apply biophysical cues to control BC proliferation and (ii) visualize in vivo early BC bone metastasis. I will now address this outstanding challenge with a multidisciplinary approach and 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, and 4) prove my hypothesis with dormancy-on-a-chip devices. 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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- engineering and technologyother engineering and technologiesmicrotechnologylab on a chip
- natural sciencesphysical sciencesopticsmicroscopy
- medical and health sciencesclinical medicineoncologybreast cancer
- natural sciencesmathematicsapplied mathematicsgame theory
- engineering and technologyindustrial biotechnologybiomaterials
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
20014 DONOSTIA-SAN SEBASTIAN
Spain