1. Academic Validation
  2. Generation of prostate cancer assembloids modeling the patient-specific tumor microenvironment

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

  • PLoS Genet. 2025 Mar 31;21(3):e1011652. doi: 10.1371/journal.pgen.1011652.
Juhee Lee 1 Yunhee Kim 1 2 Cheol Lee 3 Seong Soo Jeon 4 Hae Seo 5 Jongwon Lee 5 Jungmin Choi 5 Minyong Kang 4 6 Eunjee Kim 1 Kunyoo Shin 1 2
Affiliations

Affiliations

  • 1 Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea.
  • 2 School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
  • 3 Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 4 Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  • 5 Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
  • 6 Department of Health Sciences and Technology, The Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.
Abstract

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.

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