PDX-Derived Organoids: Insights into Cancer Stem Cells and Metastasis

Autors:

Nicolas Ancellin, Olivier Duchamp, Didier Grillot, Kenny Herry, Nicolas Legrand, Caroline Mignard

Abstract :

Patient-derived xenograft (PDX) organoids (PDXOs) are emerging as powerful tools for studying cancer biology and advancing therapeutic discovery. In this study, wereport the generation of PDX-derived organoids from pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) PDX models, establishing a translationalframework for personalized cancer research.

A key focus was the detection and enrichment of cancer stem cells (CSCs) within colorectal cancer PDXOs (CR PDXOs). Through optimized culture conditions, weachieved a remarkable 30-fold enrichment of CSCs, a pivotal population driving tumor progression, therapeutic resistance, and metastasis. This enrichment highlightsthe utility of PDXOs in dissecting stem cell biology and targeting CSC-associated mechanisms.

In conclusion, our study highlights the versatility and translational relevance of PDXOs in cancer research. By generating PDXOs from diverse models, enriching CSCpopulations, and employing advanced genetic tools for functional studies, we demonstrate the utility of PDXOs in capturing tumor complexity. The reimplantationexperiments and detection of metastasis further validate PDXOs as robust systems bridging in vitro and in vivo research. This integrated approach offers criticalinsights into tumor biology, therapeutic responses, and metastatic behavior, paving the way for improved drug discovery and personalized treatment strategies.

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