English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Engineered organoids by sequential introduction of key mutations could help modeling the dynamic cancer progression. However, it remains difficult to determine gene paths which were sufficient to capture cancer behaviors and to broadly explain cancer mechanisms. Here, as a case study of colorectal cancer (CRC), functional and dynamic characterizations of five types of engineered organoids with different mutation combinations of five driver genes ( APC, SMAD4, KRAS, TP53 , and  PIK3CA ) showed that sequential introductions of all five driver mutations could induce enhanced activation of more hallmark signatures, tending to cancer. Comparative analysis of engineered organoids and corresponding CRC tissues revealed sequential introduction of key mutations could continually shorten the biological distance from engineered organoids to CRC tissues. Nevertheless, there still existed substantial biological gaps between the engineered organoid even with five key mutations and CRC samples. Thus, we proposed an integrative strategy to prioritize gene cascading paths for shrinking biological gaps between engineered organoids and CRC tissues. Our results not only recapitulated the well-known adenoma–carcinoma sequence model (e.g., AKST-organoid with driver mutations in  APC, KRAS, SMAD4 , and  TP53 ), but also provided potential paths for delineating alternative pathogenesis underlying CRC populations (e.g., A-organoid with  APC  mutation). Our strategy also can be applied to both organoids with more mutations and other cancers, which can improve and innovate mechanism across cancer patients for drug design and cancer therapy.

Prioritizing Gene Cascading Paths to Model Colorectal Cancer Through Engineered Organoids