Generation of prostate cancer assembloids modeling the patient-specific tumor microenvironment
J.-H. Lee, Yun‐Hee Kim, Cheolmin Matthew Lee, Seong Soo Jeon, H.K. Seo, Jong Won Lee, Jungmin Choi, Minyong Kang, Eunjee Kim, Kunyoo Shin
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.