The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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Lorenzo-Martín, L.F., Hübscher, T. et al. Nature. 629, 450–457 (2024).
doi: 10.1038/s41586-024-07330-2.
Summary of the findings
Summary of the findingsThe transition from healthy to cancerous tissue is a complex and still poorly understood
process. This limited understanding of cancer initiation is largely due to the difficulty of modeling tumorigenesis in the laboratory. Although conventional cancer models are useful to study simple cancer cell behaviors, they lack the cellular diversity, tissue organization, longevity, and experimental versatility that are needed to capture the intricacies of tumorigenesis.
process. This limited understanding of cancer initiation is largely due to the difficulty of modeling tumorigenesis in the laboratory. Although conventional cancer models are useful to study simple cancer cell behaviors, they lack the cellular diversity, tissue organization, longevity, and experimental versatility that are needed to capture the intricacies of tumorigenesis.
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To solve this problem, we have developed a cancer model that can capture tumorigenesis ex vivo. We have used advanced microfabrication, tissue engineering, and optogenetic techniques to achieve this. Specifically, we have genetically engineered healthy colon epithelial cells to acquire cancerous mutations when exposed to blue light. These inducible cells have then been cultured in a microfluidic device designed to support the formation of long-lived miniature colon tissues (“mini-colons”) with in vivo-like structure.
To solve this problem, we have developed a cancer model that can capture tumorigenesis ex vivo. We have used advanced microfabrication, tissue engineering, and optogenetic techniques to achieve this. Specifically, we have genetically engineered healthy colon epithelial cells to acquire cancerous mutations when exposed to blue light. These inducible cells have then been cultured in a microfluidic device designed to support the formation of long-lived miniature colon tissues (“mini-colons”) with in vivo-like structure.
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This combination of techniques has enabled us to trigger oncogenic mutations in specific regions of “lab-made” colon epithelia, which we could then track in real-time and at single-cell resolution. This has enabled us to follow the progression of mutated cells from early-stage hyperplasias to full-blown tumors, capturing the tumorigenic process in
unprecedented detail.
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This combination of techniques has enabled us to trigger oncogenic mutations in specific regions of “lab-made” colon epithelia, which we could then track in real-time and at single-cell resolution. This has enabled us to follow the progression of mutated cells from early-stage hyperplasias to full-blown tumors, capturing the tumorigenic process in
unprecedented detail.
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Future impact
This system opens many new experimental possibilities, previously only possible in vivo. For example, it allows realistic modeling of how microbiota-derived metabolites and dietary components influence colon cancer. It also offers unparalleled resolution to study niche-specific factors in tumorigenesis. For instance, we have recently discovered the role of a glutathione peroxidase in regulating stemness and tumorigenic potential of colon cells. Ultimately, we believe that this system will enhance our understanding of the intrinsic and microenvironmental factors that drive tumor formation and progression.
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