ArticleThe Journal of clinical investigation2022
3D imaging analysis on an organoid-based platform guides personalized treatment in pancreatic ductal adenocarcinoma.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
- Review
- Current Advances in Preclinical Patient-Derived Cultivation Models for Individualized Drug Response Prediction in Pancreatic Cancer.Oncology research · 2026Review
- Constructing an ultrasound-assisted organoid model for tumor management.Discover oncology · 2025Review
- Targeted NAT10 Degradation by PROTAC NP1192 Suppresses Hypoxia-Adaptive Glycolysis and Reinvigorates CD8ACS central science · 2025Article
- Breakthroughs and challenges of organoid models for assessing cancer immunotherapy: a cutting-edge tool for advancing personalised treatments.Cell death discovery · 2025Review
- Adenine base editing of CFTR using receptor targeted nanoparticles restores function to G542X cystic fibrosis airway epithelial cells.Cellular and molecular life sciences : CMLS · 2025Article
- Organoid-based precision medicine in pancreatic cancer.United European gastroenterology journal · 2025Review
- Identification and culture of functional salivary gland ductal epithelial cells.Histochemistry and cell biology · 2024Article
- New insights of DsbA-L in the pathogenesis of metabolic diseases.Molecular and cellular biochemistry · 2024Review
- Harnessing the power of artificial intelligence for human living organoid research.Bioactive materials · 2024Review
- Auranofin as a Novel Anticancer Drug for Anaplastic Thyroid Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Review
- Patient-Derived Organoids as Therapy Screening Platforms in Cancer Patients.Advanced healthcare materials · 2024Review
- A Convexity-Preserving Level-Set Method for the Segmentation of Tumor Organoids.Bioengineering (Basel, Switzerland) · 2024Article
- Three-dimensional structural and metric characterisation of cardioids.Frontiers in cell and developmental biology · 2024Article
- Spatial Multiplexing and Omics.Nature reviews. Methods primers · 2024Article
- Construction of tumor organoids and their application to cancer research and therapy.Theranostics · 2024Review
- Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P < 0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).
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