Skip to content

EPFL scientists create lab-grown mini-colons to advance colorectal cancer research

Life sciences

29 April 2024

Researchers at the EPFL have engineered lab-grown mini-colons that replicate the development of colorectal tumors with high fidelity. Tumor development in a mini-colon. | © L. F. Lorenzo-Martín (EPFL)

Researchers at the EPFL have engineered lab-grown mini-colons that replicate the development of colorectal tumors with high fidelity.

Traditionally, cancer research has relied on animal models and cell cultures that fall short of replicating the complex cellular behaviors and tissue structures of human tumors. Even advanced organoids—small, lab-grown versions of organs—have not adequately mimicked these crucial aspects. The mini-colons developed by EPFL, however, offer a closer approximation of the cellular diversity and architectural features of actual colon tissues, both in healthy and diseased states.

The research, detailed in a recent publication in Nature, was led by Luis Francisco Lorenzo Martín and Tania Hübscher under the guidance of Matthias Lütolf at EPFL, in collaboration with Freddy Radtke and partners at Roche’s Institute of Human Biology. These mini-colons not only recreate the physical structure of the colon, including its crypt-and-lumen architecture, but also mirror the cellular variety present during the onset and progression of colorectal cancer.

A notable aspect of these mini-colons is their incorporation of optogenetics, a technique that uses light to control biological processes like gene expression. By employing a blue-light-responsive system, the researchers can induce oncogenic mutations at targeted locations within the mini-colons. “In essence, we used light to trigger tumorigenesis by turning on oncogenic driver mutations in a spatiotemporally controlled manner in healthy bioengineered colon epithelial organoids,” explained Matthias Lütolf, who is also the founding director of Roche’s new Institute of Human Biology.

Accelerating the discovery and development of effective cancer treatments

This method allows for the precise activation of oncogenes and provides a dynamic way to observe tumor formation and progression in real-time. The controlled environment of the mini-colons enables detailed analyses of tumor development and the cellular responses to mutations, offering insights into the molecular and cellular mechanisms of cancer.

Furthermore, by manipulating genetic and environmental conditions, the team has been able to simulate various tumor behaviors and identify critical factors influencing cancer progression, such as the protein GPX2, which is associated with stem cell characteristics and tumor growth.

This breakthrough enhances the potential for understanding the underlying mechanisms of colorectal cancer and testing new therapies more effectively. The ability of the mini-colons to mimic real tumor dynamics could lessen the reliance on animal models, potentially accelerating the discovery and development of effective cancer treatments.