Citations to this article
Ling Huang, … , Manuel Hidalgo, Senthil K. Muthuswamy
Published September 29, 2020
Citation Information: JCI Insight. 2020;5(21):e135544. https://doi.org/10.1172/jci.insight.135544.
Citation Information: JCI Insight. 2020;5(21):e135544. https://doi.org/10.1172/jci.insight.135544.
Abstract
Patient-derived organoid models are proving to be a powerful platform for both basic and translational studies. Here we conduct a methodical analysis of pancreatic ductal adenocarcinoma (PDAC) tumor organoid drug response in paired patient-derived xenograft (PDX) and PDX-derived organoid (PXO) models grown under WNT-free culture conditions. We report a specific relationship between area under the curve value of organoid drug dose response and in vivo tumor growth, irrespective of the drug treatment. In addition, we analyzed the glycome of PDX and PXO models and demonstrate that PXOs recapitulate the in vivo glycan landscape. In addition, we identify a core set of 57 N-glycans detected in all 10 models that represent 50%–94% of the relative abundance of all N-glycans detected in each of the models. Last, we developed a secreted biomarker discovery pipeline using media supernatant of organoid cultures and identified potentially new extracellular vesicle (EV) protein markers. We validated our findings using plasma samples from patients with PDAC, benign gastrointestinal diseases, and chronic pancreatitis and discovered that 4 EV proteins are potential circulating biomarkers for PDAC. Thus, we demonstrate the utility of organoid cultures to not only model in vivo drug responses but also serve as a powerful platform for discovering clinically actionable serologic biomarkers.
Authors
Ling Huang, Bruno Bockorny, Indranil Paul, Dipikaa Akshinthala, Pierre-Oliver Frappart, Omar Gandarilla, Arindam Bose, Veronica Sanchez-Gonzalez, Emily E. Rouse, Sylvain D. Lehoux, Nicole Pandell, Christine M. Lim, John G. Clohessy, Joseph Grossman, Raul Gonzalez, Sofia Perea Del Pino, George Daaboul, Mandeep S. Sawhney, Steven D. Freedman, Alexander Kleger, Richard D. Cummings, Andrew Emili, Lakshmi B. Muthuswamy, Manuel Hidalgo, Senthil K. Muthuswamy
Citation information
Citations to this article (63)
| Title and authors | Publication | Year |
|---|---|---|
|
Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
Feng QS, Shan XF, Yau V, Cai ZG, Xie S |
Pharmaceuticals | 2025 |
|
Tumor organoids in cancer medicine: from model systems to natural compound screening
Cong R, Lu C, Li X, Xu Z, Wang Y, Sun S |
Pharmaceutical Biology | 2025 |
|
Establishing Pancreatic Cancer Organoids from EUS-Guided Fine-Needle Biopsy Specimens
Wang MJ, Gao C, Huang X, Wang M, Zhang S, Gao XP, Zhong CQ, Li LY |
Cancers | 2025 |
|
Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy
Hai-Shan Ye, Dan Zhou, Hong Li, Jin Lv, Hui-Qi Huang, Jia-Jun She, Jun-Hua Nie, Ting-Ting Li, Meng-Di Lu, Bo-Le Du, Shu-Qing Yang, Pei-Xian Chen, Sheng Li, Guo-Lin Ye, Wei Luo, Jia Liu |
British Journal of Cancer | 2024 |
|
The impact of extracellular matrix on the precision medicine utility of pancreatic cancer patient-derived organoids
Jan Lumibao, Shira R Okhovat, Kristina L Peck, Xiaoxue Lin, Kathryn Lande, Jingjing Zou, Dannielle Engle |
JCI Insight | 2024 |
|
ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma
Benitz S, Steep A, Nasser M, Preall J, Mahajan UM, McQuithey H, Loveless I, Davis ET, Wen HJ, Long DW, Metzler T, Zwernik S, Louw M, Rempinski D, Salas-Escabillas D, Brender S, Song L, Huang L, Zhang Z, Steele NG, Regel I, Bednar F, Crawford HC |
2024 | |
|
Advancements in preclinical models of pancreatic cancer
Salu P, Reindl KM |
Pancreas | 2024 |
|
Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine
Qu S, Xu R, Yi G, Li Z, Zhang H, Qi S, Huang G |
2024 | |
|
Establishing conditions for the generation and maintenance of estrogen receptor-positive organoid models of breast cancer.
Oliphant MUJ, Akshinthala D, Muthuswamy SK |
Breast Cancer Research | 2024 |
|
Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.
Yuan Q, Shi Y, Zhang Y, Shi Y, Hussain Z, Zhao J, Jiang Y, Qiao Y, Guo Y, Lu J, Dong Z, Dong Z, Wang J, Liu K |
Cancer Cell International | 2024 |
|
Lead Compound Development of SRC-3 Inhibitors with Improved Pharmacokinetic Properties and Anticancer Efficacy
Lu D, Chen J, Qin L, Bijou I, Yi P, Li F, Song X, Mackenzie KR, Yu X, Yang B, Chowdhury SR, Korp JD, O\u2019Malley BW, Lonard DM, Wang J |
Journal of Medicinal Chemistry | 2024 |
|
Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development
Xiang D, He A, Zhou R, Wang Y, Xiao X, Gong T, Kang W, Lin X, Wang X, Liu L, Chen YG, Gao S, Liu Y |
Theranostics | 2024 |
|
Patient-derived tumor organoids: a new avenue for preclinical research and precision medicine in oncology
Thorel L, Perréard M, Florent R, Divoux J, Coffy S, Vincent A, Gaggioli C, Guasch G, Gidrol X, Weiswald LB, Poulain L |
Experimental & molecular medicine | 2024 |
|
Somatic Mutation Profile as a Predictor of Treatment Response and Survival in Unresectable Pancreatic Ductal Adenocarcinoma Treated with FOLFIRINOX and Gemcitabine Nab-Paclitaxel
Paredes de la Fuente R, Sucre S, Ponce C, Rattani AA, Peters ML |
Cancers | 2024 |
|
The αvβ6 integrin specific virotherapy, Ad5(NULL)-A20.FCU1, selectively delivers potent "in-tumour" chemotherapy to pancreatic ductal adenocarcinoma.
Badder LM, Davies JA, Meniel VS, Marušková M, Salvador-Barbero B, Bayliss RJ, Phesse TJ, Hogan C, Parker AL |
British journal of cancer | 2024 |
|
Clinical-proteomic classification and precision treatment strategy of chordoma
Yin H, Hu J, Gao J, Su T, Jin J, Jiang C, Yin W, Xu X, Chang Z, Sun W, Cai Z, Zhou W, Wang P, Lin J, Song D, Meng T |
Cell Reports Medicine | 2024 |
|
ROR2 Regulates Cellular Plasticity in Pancreatic Neoplasia and Adenocarcinoma.
Benitz S, Steep A, Nasser MM, Preall J, Mahajan UM, McQuithey H, Loveless I, Davis ET, Wen HJ, Long DW, Metzler T, Zwernik S, Louw M, Rempinski D, Salas-Escabillas DJ, Brender SM, Song L, Huang L, Theisen BK, Zhang Z, Steele NG, Regel I, Bednar F, Crawford HC |
Cancer discovery | 2024 |
|
Utility of patient-derived xenografts to evaluate drug sensitivity and select optimal treatments for individual non-small-cell lung cancer patients.
Wang X, Zhu J, Li L, Zhao Q, Huang Y, Wen C, Chen D, Wu L |
Molecular medicine (Cambridge, Mass.) | 2024 |
|
Breaking the mold: 3D cell cultures reshaping the future of cancer research
Cordeiro S, Oliveira BB, Valente R, Ferreira D, Luz A, Baptista PV, Fernandes AR |
Frontiers in Cell and Developmental Biology | 2024 |
|
A large-scale proteomics resource of circulating extracellular vesicles for biomarker discovery in pancreatic cancer
Bockorny B, Muthuswamy L, Huang L, Hadisurya M, Maria Lim C, Tsai LL, Gill RR, Wei JL, Bullock AJ, Grossman JE, Besaw RJ, Narasimhan S, Tao WA, Perea S, Sawhney MS, Freedman SD, Hildago M, Iliuk A, Muthuswamy SK |
eLife | 2024 |
|
A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial
Sarno F, Tenorio J, Perea S, Medina L, Pazo-Cid R, Juez I, Garcia-Carbonero R, Feliu J, Guillen-Ponce C, Lopez-Casas PP, Guerra C, Duran Y, López-Acosta JF, Alonso C, Esquivel E, Dopazo A, Akshinthala D, Muthuswamy SK, Lapunzina P, Bockorny B, Hidalgo M |
Clinical Cancer Research | 2024 |
|
Organoid‐based precision medicine in pancreatic cancer
Beutel AK, Ekizce M, Ettrich TJ, Seufferlein T, Lindenmayer J, Gout J, Kleger A |
United European Gastroenterology Journal | 2024 |
|
Recent Advances in Well-Designed Therapeutic Nanosystems for the Pancreatic Ductal Adenocarcinoma Treatment Dilemma
Yang XY, Lu YF, Xu JX, Du YZ, Yu RS |
Molecules (Basel, Switzerland) | 2023 |
|
The functional and clinical roles of liquid biopsy in patient-derived models
Zhu Z, Hu E, Shen H, Tan J, Zeng S |
Journal of Hematology & Oncology | 2023 |
|
A Large-Scale Proteomics Resource of Circulating Extracellular Vesicles for Biomarker Discovery in Pancreatic Cancer
Bockorny B, Muthuswamy L, Huang L, Hadisurya M, Lim CM, Tsai LL, Gill RR, Wei JL, Bullock AJ, Grossman JE, Besaw RJ, Narasimhan S, Tao WA, Perea S, Sawhney MS, Freedman SD, Hidalgo M, Iliuk A, Muthuswamy SK |
2023 | |
|
Patient-derived xenograft models in cancer therapy: technologies and applications
Liu Y, Wu W, Cai C, Zhang H, Shen H, Han Y |
Signal Transduction and Targeted Therapy | 2023 |
|
Establishment and Culture of Patient-Derived Breast Organoids.
Aggarwal D, Russo S, Naik P, Bhatia S, Spector DL |
Journal of visualized experiments : JoVE | 2023 |
|
The role of nanotherapy in head and neck squamous cell carcinoma by targeting tumor microenvironment
Zhang Y, Dong P, Yang L |
Frontiers in immunology | 2023 |
|
Micro-engineering and nano-engineering approaches to investigate tumour ecosystems.
Kim M, Panagiotakopoulou M, Chen C, Ruiz SB, Ganesh K, Tammela T, Heller DA |
Nature reviews. Cancer | 2023 |
|
Functional and Clinical Proteomic Exploration of Pancreatic Cancer
Huang P, Gao W, Fu C, Tian R |
Molecular & cellular proteomics : MCP | 2023 |
|
SENP5 promotes homologous recombination-mediated DNA damage repair in colorectal cancer cells through H2AZ deSUMOylation.
Liu T, Wang H, Chen Y, Wan Z, Du Z, Shen H, Yu Y, Ma S, Xu Y, Li Z, Yu N, Zhang F, Cao K, Cai J, Zhang W, Gao F, Yang Y |
Journal of experimental & clinical cancer research : CR | 2023 |
|
Establishing conditions for the generation and maintenance of estrogen receptor-positive organoid models of breast cancer
Oliphant MU, Akshinthala D, Muthuswamy SK |
Research square | 2023 |
|
Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment
Alipourgivi F, Motolani A, Qiu AY, Qiang W, Yang GY, Chen S, Lu T |
International journal of molecular sciences | 2023 |
|
Patient-derived organoids as a personalized selection tool for targeted therapy in patients with gastrointestinal cancers
Tara Hogenson, Hao Xie, William Phillips, Merih D Toruner, Jenny J. Li, Isaac Horn, Devin Kennedy, Luciana Almada, David Marks, Murat Toruner, Ashley Sigafoos, Amanda Koenig, Rachel Olson, Ezequiel Tolosa, Cheng Zhang, Hu Li, Jonathan Bleeker, Michael Barrett, James Boyum, Benjamin Kipp, Amit Mahipal, Joleen Hubbard, Temperance Scheffler, Gloria Petersen, Surendra Dasari, Ann Oberg, Mark Truty, Michael Levy, Mojun Zhu, Daniel Billadeau, Alex Adjei, Nelson Dusetti, Juan Iovanna, Tanios Bekaii-Saab, Wen Ma, Martin Fernandez-Zapico |
JCI Insight | 2022 |
|
Proteomic analysis distinguishes extracellular vesicles produced by cancerous versus healthy pancreatic organoids
A Buenafe, C Dorrell, A Reddy, J Klimek, D Marks |
Scientific Reports | 2022 |
|
Tumor organoids: applications in cancer modeling and potentials in precision medicine
H Xu, D Jiao, A Liu, K Wu |
Journal of Hematology & Oncology | 2022 |
|
Human expandable pancreatic progenitor–derived β cells ameliorate diabetes
Ma X, Lu Y, Zhou Z, Li Q, Chen X, Wang W, Jin Y, Hu Z, Chen G, Deng Q, Shang W, Wang H, Fu H, He X, Feng XH, Zhu S |
Science Advances | 2022 |
|
Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer
Grossman JE, Muthuswamy L, Huang L, Akshinthala D, Perea S, Gonzalez RS, Tsai LL, Cohen J, Bockorny B, Bullock AJ, Schlechter B, Peters ML, Conahan C, Narasimhan S, Lim C, Davis RB, Besaw R, Sawhney MS, Pleskow D, Berzin TM, Smith M, Kent TS, Callery M, Muthuswamy SK, Hidalgo M |
Clinical cancer research | 2022 |
|
Multicellular Modelling of Difficult-to-Treat Gastrointestinal Cancers: Current Possibilities and Challenges
Hakuno SK, Michiels E, Kuhlemaijer EB, Rooman I, Hawinkels LJ, Slingerland M |
International journal of molecular sciences | 2022 |
|
Patient Derived Ex-Vivo Cancer Models in Drug Development, Personalized Medicine, and Radiotherapy
Zitter R, Chugh RM, Saha S |
Cancers | 2022 |
|
Functional Drug Screening in the Era of Precision Medicine
Napoli GC, Figg WD, Chau CH |
Frontiers in Medicine | 2022 |
|
Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?
Gao Y, Kruithof-de Julio M, Peng RW, Dorn P |
Cancers | 2022 |
|
Extracellular vesicles and particles impact the systemic landscape of cancer
Lucotti S, Kenific CM, Zhang H, Lyden D |
The EMBO Journal | 2022 |
|
Applications of human organoids in the personalized treatment for digestive diseases
Wang Q, Guo F, Jin Y, Ma Y |
Signal Transduction and Targeted Therapy | 2022 |
|
Targeting DNA Repair with Combined Inhibition of NHEJ and MMEJ Induces Synthetic Lethality in TP53-Mutant Cancers.
Patterson-Fortin J, Bose A, Tsai WC, Grochala C, Nguyen H, Zhou J, Parmar K, Lazaro JB, Liu J, McQueen K, Shapiro GI, Kozono D, D'Andrea AD |
Cancer research | 2022 |
|
3D organ-on-a-chip: The convergence of microphysiological systems and organoids
Baptista LS, Porrini C, Kronemberger GS, Kelly DJ, Perrault CM |
Frontiers in Cell and Developmental Biology | 2022 |
|
Screening of an individualized treatment strategy for an advanced gallbladder cancer using patient-derived tumor xenograft and organoid models
Tan D, An J, Gong M, Wang H, Li H, Meng H, Zhang C, Zhao Y, Ge X, Shi C |
Frontiers in Oncology | 2022 |
|
Role of Patient-Derived Models of Cancer in Translational Oncology
Idrisova KF, Simon HU, Gomzikova MO |
Cancers | 2022 |
|
In vivo antitumor efficacy of 17-AAG loaded PMMA in a human multiple myeloma xenograft mouse model.
Shi X, Wei Y, Yao X, Du B, Wu X, Kong X, Du X |
Clinical and Experimental Medicine | 2022 |
|
Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages
A Poggi, F Villa, JL Fernadez, D Costa, MR Zocchi, R Benelli |
Cancers | 2021 |
|
3D Cell Cultures as Prospective Models to Study Extracellular Vesicles in Cancer
G Bordanaba-Florit, I Madarieta, B Olalde, JM Falcón-Pérez, F Royo |
Cancers | 2021 |
|
A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response
AK Beutel, L Schütte, J Scheible, E Roger, M Müller, L Perkhofer, AM Kestler, JM Kraus, HA Kestler, TF Barth, J Lemke, M Kornmann, TJ Ettrich, J Gout, T Seufferlein, A Kleger |
Cancers | 2021 |
|
Exploring the Complementarity of Pancreatic Ductal Adenocarcinoma Preclinical Models
Hoare O, Fraunhoffer N, Elkaoutari A, Gayet O, Bigonnet M, Roques J, Nicolle R, McGuckin C, Forraz N, Sohier E, Tonon L, Wajda P, Boyault S, Attignon V, Tabone-Eglinger S, Barbier S, Mignard C, Duchamp O, Iovanna J, Dusetti NJ |
Cancers | 2021 |
|
Human Organoid and Supporting Technologies for Cancer and Toxicological Research
Sekine K |
Frontiers in Genetics | 2021 |
|
The somatic molecular evolution of cancer: Mutation, selection, and epistasis
Dasari K, Somarelli JA, Kumar S, Townsend JP |
Progress in Biophysics and Molecular Biology | 2021 |
|
Application of Organoid Models in Prostate Cancer Research
Zhou L, Zhang C, Zhang Y, Shi C |
Frontiers in Oncology | 2021 |
|
Novel 3D µtissues Mimicking the Fibrotic Stroma in Pancreatic Cancer to Study Cellular Interactions and Stroma-Modulating Therapeutics
Pednekar KP, Heinrich MA, van Baarlen J, Prakash J |
Cancers | 2021 |
|
Empirical identification and validation of tumor-targeting T cell receptors from circulation using autologous pancreatic tumor organoids
Meng Q, Xie S, Gray GK, Dezfulian MH, Li W, Huang L, Akshinthala D, Ferrer E, Conahan C, Perea Del Pino S, Grossman J, Elledge SJ, Hidalgo M, Muthuswamy SK |
Journal for ImmunoTherapy of Cancer | 2021 |
|
Relevance of biopsy-derived pancreatic organoids in the development of efficient transcriptomic signatures to predict adjuvant chemosensitivity in pancreatic cancer.
Nicolle R, Gayet O, Bigonnet M, Roques J, Chanez B, Puleo F, Augustin J, Emile JF, Svrcek M, Arsenijevic T, Hammel P, Rebours V, Giovannini M, Grandval P, Dahan L, Moutardier V, Mitry E, Van Laethem JL, Bachet JB, Cros J, Iovanna J, Dusetti NJ |
Translational oncology | 2021 |
|
Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance.
Murphy KJ, Chambers CR, Herrmann D, Timpson P, Pereira BA |
Cancers | 2021 |
|
Organotypic Modeling of the Tumor Landscape
MM Haykal, C Nahmias, C Varon, OC Martin |
Frontiers in Cell and Developmental Biology | 2020 |
|
Drug Inhibition of SARS-CoV-2 Replication in Human Pluripotent Stem Cell–Derived Intestinal Organoids
Krüger J, Groß R, Conzelmann C, Müller JA, Koepke L, Sparrer KM, Weil T, Schütz D, Seufferlein T, Barth TF, Stenger S, Heller S, Münch J, Kleger A |
Cellular and Molecular Gastroenterology and Hepatology | 2020 |
|
Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer
Singh T, Neal AS, Moatamed NA, Memarzadeh S |
International journal of molecular sciences | 2020 |
