Generation of prostate cancer assembloids modeling the patient-specific tumor microenvironment.

Prostate cancer (PC) is the most frequently diagnosed malignancy among men and contributes significantly to cancer-related mortality. While recent advances in in vitro PC modeling systems have been made, there remains a lack of robust preclinical models that faithfully recapitulate the genetic and p...

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Main Authors: Juhee Lee, Yunhee Kim, Cheol Lee, Seong Soo Jeon, Hae Seo, Jongwon Lee, Jungmin Choi, Minyong Kang, Eunjee Kim, Kunyoo Shin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-03-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1011652
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Summary:Prostate cancer (PC) is the most frequently diagnosed malignancy among men and contributes significantly to cancer-related mortality. While recent advances in in vitro PC modeling systems have been made, there remains a lack of robust preclinical models that faithfully recapitulate the genetic and phenotypic characteristics across various PC subtypes-from localized PC (LPC) to castration-resistant PC (CRPC)-along with associated stromal cells. Here, we established human PC assembloids from LPC and CRPC tissues by reconstituting tumor organoids with corresponding cancer-associated fibroblasts (CAFs), thereby incorporating aspects of the tumor microenvironment (TME). Established PC organoids exhibited high concordance in genomic landscape with parental tumors, and the tumor assembloids showed a higher degree of phenotypic similarity to parental tumors compared to tumor organoids without CAFs. PC assembloids displayed increased proliferation and reduced sensitivity to anti-cancer treatments, indicating that PC assembloids are potent tools for understanding PC biology, investigating the interaction between tumor and CAFs, and identifying personalized therapeutic targets.
ISSN:1553-7390
1553-7404