Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies owing to late diagnosis, extensive intratumoral heterogeneity, a dense desmoplastic tumor microenvironment, and limited therapeutic responsiveness. Although current treatment regimens, including FOLFIRINOX and gemcitabine plus nab-paclitaxel, have modestly improved survival, chemoresistance and the lack of reliable predictive biomarkers continue to hinder precision oncology. Conventional two-dimensional cell lines and many in vivo models do not fully recapitulate the complex architecture, cellular interactions, and biological heterogeneity of human PDAC. Patient-derived organoids (PDOs) have emerged as physiologically relevant three-dimensional models that preserve the genetic, molecular, and phenotypic characteristics of the original tumor while enabling rapid ex vivo pharmacotyping and functional therapeutic evaluation. This review summarizes recent advances in PDAC organoid technology, including tissue acquisition, organoid establishment, molecular characterization, biobanking, and integration with cancer-associated fibroblasts, immune cells, endothelial cells, CRISPR/Cas9 genome editing, assembloid systems, and microfluidic organ-on-chip platforms. We further discuss the applications of PDOs in drug screening, molecular subtype characterization, modeling therapeutic resistance, and supporting precision treatment strategies, together with emerging evidence from prospective clinical studies. Finally, we critically examine the remaining translational challenges, including culture-induced phenotypic drift, limited microenvironmental complexity, interlaboratory variability, assay standardization, and regulatory implementation. Although PDOs represent promising platforms for functional precision oncology, widespread clinical adoption will require standardized methodologies, prospective multicenter validation, and regulatory qualification before routine integration into clinical decision-making.
Hee-Seung Lee, B. Koo· Cancer Biome and Targeted Th...· 0 citations
Metastatic disease remains the leading cause of cancer-related death, yet most precision oncology strategies still emphasize profiling primary tumors and tracking cell-free tumor DNA (ctDNA). Although ctDNA has transformed genomic profiling, molecular residual disease monitoring, and early cancer detection, it cannot directly capture viable tumor cell states, phenotypic plasticity, or functional adaptations that drive metastatic spread. We propose that the next phase of precision oncology should integrate the cellular dimension of metastasis through systematic circulating tumor cell (CTC) profiling. The SCRUM-MONSTAR platform, one of the largest pan-cancer molecular profiling initiatives in Japan, offers an exceptional foundation for this transition through its nationwide infrastructure for multi-omics analysis, longitudinal biospecimen collection, and artificial intelligence-enabled clinical interpretation. By combining matched tissue profiling, serial ctDNA analysis, single-cell CTC transcriptomics, metabolomics, and organoid- and mouse-based functional modeling, SCRUM-MONSTAR-CTC could evolve into a translational ecosystem for anti-metastatic drug discovery. Within this framework, we highlight adherent-to-suspension transition (AST) as one representative, experimentally tractable plasticity program that enables tumor cells to survive in circulation and subsequently colonize distant organs. We envision that identifying and therapeutically targeting AST-related and other metastatic plasticity programs across tumor types will provide a path toward clinically actionable anti-metastatic therapies. More broadly, this framework could enable the identification of metastatic vulnerabilities, the development of biomarker-guided anti-metastatic trials, and the reverse translation of patient-derived discoveries into early-phase clinical testing. Precision oncology must move beyond cataloging tumor genomes and begin targeting metastasis as a dynamic biological process. UMIN000056873, approved by the Institutional Review Board of the National Cancer Center Hospital East.
T. Hashimoto, T. Shibuki, T. Fujisawa et al.· International Journal of Cli...· 0 citations
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