Metastasis—the spread of cancer from a primary tumor to distant organs—remains one of the most complex and least understood aspects of cancer progression, responsible for over 90% of cancer-related deaths. A key step in this process is the migration of circulating tumor cells (CTCs) through the heterogeneous and mechanically complex environments of the extracellular matrix (ECM) and microvasculature. Despite its clinical significance, the physical and mechanical factors governing CTC transport, deformation, and retention in these environments remain largely unexplored. Traditional cancer research has focused predominantly on genetic and biochemical signaling pathways, leaving a gap in our understanding of the physical forces and fluid dynamic conditions that influence metastasis.
The ORION project was designed to fill this critical knowledge gap by investigating how hydrodynamic forces, microstructural heterogeneity, and mechanobiological properties of tumor cells interact to govern their migration behavior. The overarching objective was to develop a fundamental understanding of CTC transport through confined porous environments, using a combination of microfluidic experimentation, computational fluid dynamics (CFD), rheological modeling, and mechanobiology. By integrating these approaches, ORION aimed to reveal the physical principles underlying key metastatic behaviors such as cell trapping, deformation, collective motility, and the response to chemotactic gradients like TGF-β.
The expected impact of ORION extends across multiple domains. Scientifically, the project contributes a novel and quantifiable framework for studying cancer cell transport in complex microenvironments. Biomedically, the insights gained can help building new strategies for early detection of metastatic potential, improve therapeutic targeting, and inspire bioengineered platforms for drug testing or cell sorting. Industrially, the findings offer pathways toward the development of microfluidic systems for diagnostic or therapeutic use. Societally, understanding and ultimately disrupting the physical mechanisms of metastasis could lead to measurable improvements in patient survival and reduce the burden on healthcare systems.
Situated within the broader strategic landscape of Horizon Europe and the EU’s Mission on Cancer, ORION supports the goal of reducing the societal impact of cancer by contributing to upstream prevention and more effective treatment strategies. Its interdisciplinary and translational nature aligns with Europe's commitment to cross-sectoral, high-impact biomedical innovation. While social sciences and humanities were not explicitly integrated into this project, ORION’s focus on public health relevance and its potential to influence clinical practice make it highly aligned with societal priorities in healthcare.
