Patient-derived mini-colons enable long-term modeling of tumor-microenvironment complexity.

Details

Serval ID
serval:BIB_6FBB2EBCBF0E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Patient-derived mini-colons enable long-term modeling of tumor-microenvironment complexity.
Journal
Nature biotechnology
Author(s)
Lorenzo-Martín L.F., Broguiere N., Langer J., Tillard L., Nikolaev M., Coukos G., Homicsko K., Lutolf M.P.
ISSN
1546-1696 (Electronic)
ISSN-L
1087-0156
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization, biological durability and experimental flexibility. Thus, many multifactorial cancer processes, especially those involving the tumor microenvironment, are difficult to study ex vivo. To overcome these limitations, we herein implemented tissue-engineering and microfabrication technologies to develop topobiologically complex, patient-specific cancer avatars. Focusing on colorectal cancer, we generated miniature tissues consisting of long-lived gut-shaped human colon epithelia ('mini-colons') that stably integrate cancer cells and their native tumor microenvironment in a format optimized for real-time, high-resolution evaluation of cellular dynamics. We demonstrate the potential of this system through several applications: a comprehensive evaluation of drug effectivity, toxicity and resistance in anticancer therapies; the discovery of a mechanism triggered by cancer-associated fibroblasts that drives cancer invasion; and the identification of immunomodulatory interactions among different components of the tumor microenvironment. Similar approaches should be feasible for diverse tumor types.
Pubmed
Web of science
Create date
11/07/2024 15:43
Last modification date
26/07/2024 7:02
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