Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response

Walsh, Alex J.; Castellanos, Jason; Nagathihalli, Nagaraj S.; Merchant, Nipun B.; Skala, Melissa C.

doi:10.1097/mpa.0000000000000543

Cited by 116 publications

(159 citation statements)

References 25 publications

(55 reference statements)

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“…Organoids are representative of the primary tumor from which they are derived, and studies suggest that drug response in organoids corresponds to drug response in the host (18,20). Therefore, organoid-based high-throughput drug screening will enable testing of treatment options using patientspecific tissue.…”

Section: Organoids As a Platform For Personalized Drug Screensmentioning

confidence: 99%

“…Organoids have also been used to test drug response and evaluate novel drugs in development. Preliminary evidence suggests that organoid drug sensitivity correlates with patient outcome (5,7,9,10,(16)(17)(18)(19)(20)(21).…”

Section: Primary Human Organoids As a Model Of Cancermentioning

confidence: 99%

“…An organoid-based anticancer drug screen could identify the optimal drugs for each patient, allowing eradication of the tumor while minimizing toxicity from overtreatment and ineffective treatment. When combined with OMI, a microscopy technique sensitive to changes in cellular metabolism, response is measured as a drug-induced change in cellular metabolism (18,20). OMI allows heterogeneity analysis of response to identify nonresponding subclones.…”

Section: Organoids As a Platform For Personalized Drug Screensmentioning

confidence: 99%

“…Furthermore, light doses used for optical imaging are nonionizing and nondamaging, enabling time-course evaluation of individual organoids. High-resolution optical imaging allows cellular and subcellular analyses, enabling identification and quantification of cellular heterogeneity and behavioral heterogeneity (e.g., differential responses to treatment) within organoids (18,20).…”

Section: Optical Imaging Of Organoidsmentioning

confidence: 99%

“…Optical imaging technologies used to study organoids include bright-field microscopy, light microscopy, phase microscopy, fluorescence microscopy, confocal microscopy, time-lapse microscopy, multiphoton fluorescence imaging, fluorescence lifetime imaging, and optical coherence tomography (OCT) (8,12,(18)(19)(20)29,30). In wide-field or whole-field microscopy, an entire sample or field of view is illuminated by a light source, and images are captured by a camera.…”

Section: Optical Imaging Of Organoidsmentioning

confidence: 99%

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Functional Optical Imaging of Primary Human Tumor Organoids: Development of a Personalized Drug Screen

2017

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Primary tumor organoids are a robust model of individual human cancers and present a unique platform for patient-specific drug testing. Optical imaging is uniquely suited to assess organoid function and behavior because of its subcellular resolution, penetration depth through the entire organoid, and functional endpoints. Specifically, optical metabolic imaging (OMI) is highly sensitive to drug response in organoids, and OMI in tumor organoids correlates with primary tumor drug response. Therefore, an OMI organoid drug screen could enable accurate testing of drug response for individualized cancer treatment. The objective of this perspective is to introduce OMI and tumor organoids to a general audience in order to foster the adoption of these techniques in diverse clinical and laboratory settings.

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Section: Organoids As a Platform For Personalized Drug Screensmentioning

confidence: 99%

Section: Primary Human Organoids As a Model Of Cancermentioning

confidence: 99%

Section: Organoids As a Platform For Personalized Drug Screensmentioning

confidence: 99%

Section: Optical Imaging Of Organoidsmentioning

confidence: 99%

Section: Optical Imaging Of Organoidsmentioning

confidence: 99%

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Functional Optical Imaging of Primary Human Tumor Organoids: Development of a Personalized Drug Screen

2017

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Towards Automation in 3D Cell Culture: Selective and Gentle High‐Throughput Handling of Spheroids and Organoids via Novel Pick‐Flow‐Drop Principle

Zieger,

Frejek,

Zimmermann

et al. 2024

Adv Healthcare Materials

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Three‐dimensional (3D) cell culture is becoming increasingly important for mimicking physiological tissue structures in areas such as drug discovery and personalized medicine. To enable reproducibility on a large scale, automation technologies for standardized handling are still a challenge. Here, a novel method for fully automated size classification and handling of cell aggregates like spheroids and organoids is presented. Using microfluidic flow generated by a piezoelectric droplet generator, aggregates are aspirated from a reservoir on one side of a thin capillary and deposited on the other side, encapsulated in free‐flying nanoliter droplets to a target. The platform has aggregate aspiration and plating efficiencies of 98.1% and 98.4%, respectively, at a processing throughput of up to 21 aggregates per minute. Cytocompatibility of the method is thoroughly assessed with MCF7, LNCaP, A549 spheroids and colon organoids, revealing no adverse effects on cell aggregates as shear stress is reduced compared to manual pipetting. Further, generic size‐selective handling of heterogeneous organoid samples, single‐aggregate‐dispensing efficiencies of up to 100% and the successful embedding of spheroids or organoids in a hydrogel with subsequent proliferation is demonstrated. This platform is a powerful tool for standardized 3D in vitro research.This article is protected by copyright. All rights reserved

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Patient-derived organoid models help define personalized management of gastrointestinal cancer

Aberle

Burkhart

Tiriac

et al. 2018

British Journal of Surgery

109

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Background: The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional 'organoid' models.Methods: A PubMed search was conducted to identify relevant articles. An overview of the literature and published protocols is presented, and the implications of these models for patients with cancer, surgeons and oncologists are explained.Results: Organoid culture methods have been established for healthy and diseased tissues from oesophagus, stomach, intestine, pancreas, bile duct and liver. Because organoids can be generated with high efficiency and speed from fine-needle aspirations, biopsies or resection specimens, they can serve as a personal cancer model. Personalized treatment could become a more standard practice by using these cell cultures for extensive molecular diagnosis and drug screening. Drug sensitivity assays can give a clinically actionable sensitivity profile of a patient's tumour. However, the predictive capability of organoid drug screening has not been evaluated in prospective clinical trials. Conclusion:High-throughput drug screening on organoids, combined with next-generation sequencing, proteomic analysis and other state-of-the-art molecular diagnostic methods, can shape cancer treatment to become more effective with fewer side-effects.

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Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response

Cited by 116 publications

References 25 publications

Functional Optical Imaging of Primary Human Tumor Organoids: Development of a Personalized Drug Screen

Functional Optical Imaging of Primary Human Tumor Organoids: Development of a Personalized Drug Screen

Towards Automation in 3D Cell Culture: Selective and Gentle High‐Throughput Handling of Spheroids and Organoids via Novel Pick‐Flow‐Drop Principle

Patient-derived organoid models help define personalized management of gastrointestinal cancer

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