Being able to detect cancers at an early stage often means better treatment outcomes and survival rates. However, the lack of clinical samples from early-stage tumors makes it difficult to identify disease-relevant biomarkers and to understand the conditions that drive malignant transformation. High-fidelity in vitro models of early cancer that provide mechanistic insight into tumor development offer a way to bridge this gap. By faithfully recreating the conditions present during cancer initiation, these models can generate predictive knowledge to guide the development of treatments targeting cancers at their earliest stages.
In a new review published in Nature Reviews Bioengineering, researchers at Oregon Health and Science University, Stanford University, University of Cambridge explore the breadth of tissue engineering and biofabrication techniques that enable the construction of detailed in vitro models replicating early cancer conditions and tumor evolution.
In their article, Luiz Bertassoni and colleagues highlight the benefits of shifting from the conventional cancer treatment paradigm focused on eliminating malignant cells, to one aimed at altering disease progression before malignancy arises. Early-stage models that capture the gradual transformation of healthy tissues into malignant ones and enable a deeper understanding of oncogenesis are central to this transition toward a more preventive approach to cancer treatment.
Here, high-precision biofabrication tools play an important role in facilitating this transition by recreating the pre-malignant tissue microenvironment with high fidelity. These engineered tissue models provide much greater experimental control compared to animal models, allowing researchers to directly study how different stressors influence tissue behavior and cancer initiation. In this way, bioengineered models can yield a mechanistic understanding of cancer development and help identify key biomarkers of early disease.
Bertassoni and colleagues emphasize that biofabrication methods should not be viewed in isolation. Techniques such as bioprinting, organoids, and organ-on-a-chip systems each have distinct strengths and together provide a more complete picture when used in combination.
For applications requiring the highest level of precision—such as investigating specific cellular interactions—microfluidic bioprinting technologies with single-cell resolution, including Fluicell’s Biopixlar, offer a powerful option. This technique enables the creation of heterogeneous tissues composed of multiple cell types arranged in precisely defined patterns by directly depositing cells at target locations.
As an example, the authors describe how single-cell bioprinting has been used to reproduce breast cancer biopsies with 1.6 µm resolution. This approach even allows individual healthy cells to be selectively replaced with malignant ones, enabling real-time studies of cancer progression.
Together with complementary techniques such as light- or extrusion-based bioprinting, organoids, and organ-on-a-chip systems, microfluidic bioprinting forms part of a diverse toolset that enables researchers to address the many challenges of understanding early cancer development.
Through their review, Bertassoni and colleagues provide a clear and comprehensive overview of tissue engineering and biofabrication techniques and their potential in early cancer research. Their work serves as a roadmap for rethinking how we understand cancer development—and for shifting from treating the disease to intercepting it before it fully emerges.
Read the article Engineering and biofabrication of early cancer models in Nature Reviews Bioengineering.