P119 An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity

Kopper, Oded; Witte, CJ de; Lõhmussaar, Kadi; Valle-Inclán, Jose Espejo; Hami, Nizar; Kester, Lennart; Balgobind, AV; Korving, Jeroen; Proost, Natalie; Begthel, Harry; Wijk, LM van; Revilla, SA; Theeuwsen, Rebecca; Ven, Marieke van de; Roosmalen, MJ van; Ponsioen, Bas; Ho, Victor W.; Bg, Neel; Bosse, Tjalling; Gaarenstroom, K.N.; Vrieling, Harry; Vreeswijk, Mpg; Diest, PJ van; Witteveen, P. O.; Jonges, Trudy N.; Jl, Bos; Oudenaarden, Alexander van; Zweemer, RP; Snippert, Hjg; Kloosterman, WP

doi:10.1136/ijgc-2019-esgo.182

Cited by 19 publications

(21 citation statements)

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“…Pauli et al demonstrated the possibility of using this model, where the drugs' effects (afatinib, vorinostat, paclitaxel, carboplatin, etc.) were tested, Kopper et al also confirmed the possibility of testing the sensitivity of organoids to drugs after their subcutaneous injection in mice and Lee et al investigated therapeutic responses to treatment of bladder tumors [4,137,138]. This model will provide new preclinical data for appropriate cancer therapy selection.…”

Section: Spheroids and Organoids For Personalized Medicinementioning

confidence: 94%

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Gilazieva

Ponomarev

Rutland

et al. 2020

Cancers

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One of the promising directions in personalized medicine is the use of three-dimensional (3D) tumor models such as spheroids and organoids. Spheroids and organoids are three-dimensional cultures of tumor cells that can be obtained from patient tissue and, using high-throughput personalized medicine methods, provide a suitable therapy for that patient. These 3D models can be obtained from most types of tumors, which provides opportunities for the creation of biobanks with appropriate patient materials that can be used to screen drugs and facilitate the development of therapeutic agents. It should be noted that the use of spheroids and organoids would expand the understanding of tumor biology and its microenvironment, help develop new in vitro platforms for drug testing and create new therapeutic strategies. In this review, we discuss 3D tumor spheroid and organoid models, their advantages and disadvantages, and evaluate their promising use in personalized medicine.

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Section: Spheroids and Organoids For Personalized Medicinementioning

confidence: 94%

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Gilazieva

Ponomarev

Rutland

et al. 2020

Cancers

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“…They were then able to create intestinal organoids from patient-derived normal and colorectal cancer tissue adding Wnt, the transforming growth factor-β (TGF-β) inhibitor A83-01, and the p38 inhibitor SB202190 ( 25 ). Subsequently, PDOs were established from several types of cancer, such as pancreatic ( 15 , 26 ), prostate ( 27 , 28 ), gastric ( 29 ), and other cancers ( 20 , 21 , 30 ).…”

Section: Pc Pdos Retain Parental Cancer Featuresmentioning

confidence: 99%

Pancreatic Cancer Patient-Derived Organoid Platforms: A Clinical Tool to Study Cell- and Non-Cell-Autonomous Mechanisms of Treatment Response

et al. 2021

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For many years, cell lines and animal models have been essential to improve our understanding of the basis of cell metabolism, signaling, and genetics. They also provided an essential boost to cancer drug discovery. Nevertheless, these model systems failed to reproduce the tumor heterogeneity and the complex biological interactions between cancer cells and human hosts, making a high priority search for alternative methods that are able to export results from model systems to humans, which has become a major bottleneck in the drug development. The emergent human in vitro 3D cell culture technologies have attracted widespread attention because they seem to have the potential to overcome these limitations. Organoids are unique 3D culture models with the ability to self-organize in contained structures. Their versatility has offered an exceptional window of opportunity to approach human cancers. Pancreatic cancers (PCs) patient-derived-organoids (PDOs) preserve histological, genomic, and molecular features of neoplasms they originate from and therefore retain their heterogeneity. Patient-derived organoids can be established with a high success rate from minimal tissue core specimens acquired with endoscopic-ultrasound-guided techniques and assembled into platforms, representing tens to hundreds of cancers each conserving specific features, expanding the types of patient samples that can be propagated and analyzed in the laboratory. Because of their nature, PDO platforms are multipurpose systems that can be easily adapted in co-culture settings to perform a wide spectrum of studies, ranging from drug discovery to immune response evaluation to tumor-stroma interaction. This possibility to increase the complexity of organoids creating a hybrid culture with non-epithelial cells increases the interest in organoid-based platforms giving a pragmatic way to deeply study biological interactions in vitro. In this view, implementing organoid models in co-clinical trials to compare drug responses may represent the next step toward even more personalized medicine. In the present review, we discuss how PDO platforms are shaping modern-day oncology aiding to unravel the most complex aspects of PC.

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“…These organoids are generated from either pluripotent stem cells (PSCs) (either induced PSCs [iPSCs] or embryonic stem cells), adult stem cells (ASCs) or adult tumor tissue by self-organization. Their use for drug discovery and personalized medicine has been reviewed (11) and first proof of concept to generate personalized data has been provided (12).…”

Section: What Did Stem Cell-and Patient-derived Organoids Teach Us?mentioning

confidence: 99%

An Individual Patient's “Body” on Chips—How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach

Marx

Accastelli²,

David

et al. 2021

Front. Med.

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The first concepts for reproducing human systemic organismal biology in vitro were developed over 12 years ago. Such concepts, then called human- or body-on-a-chip, claimed that microphysiological systems would become the relevant technology platform emulating the physiology and morphology of human organisms at the smallest biologically acceptable scale in vitro and, therefore, would enable the selection of personalized therapies for any patient at unprecedented precision. Meanwhile, the first human organoids—stem cell-derived complex three-dimensional organ models that expand and self-organize in vitro—have proven that in vitro self-assembly of minute premature human organ-like structures is feasible, once the respective stimuli of ontogenesis are provided to human stem cells. Such premature organoids can precisely reflect a number of distinct physiological and pathophysiological features of their respective counterparts in the human body. We now develop the human-on-a-chip concepts of the past into an organismoid theory. We describe the current concept and principles to create a series of organismoids—minute, mindless and emotion-free physiological in vitro equivalents of an individual's mature human body—by an artificially short process of morphogenetic self-assembly mimicking an individual's ontogenesis from egg cell to sexually mature organism. Subsequently, we provide the concept and principles to maintain such an individual's set of organismoids at a self-sustained functional healthy homeostasis over very long time frames in vitro. Principles how to perturb a subset of healthy organismoids by means of the natural or artificial induction of diseases are enrolled to emulate an individual's disease process. Finally, we discuss using such series of healthy and perturbed organismoids in predictively selecting, scheduling and dosing an individual patient's personalized therapy or medicine precisely. The potential impact of the organismoid theory on our healthcare system generally and the rapid adoption of disruptive personalized T-cell therapies particularly is highlighted.

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P119 An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity

Cited by 19 publications

References 0 publications

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Pancreatic Cancer Patient-Derived Organoid Platforms: A Clinical Tool to Study Cell- and Non-Cell-Autonomous Mechanisms of Treatment Response

An Individual Patient's “Body” on Chips—How Organismoid Theory Can Translate Into Your Personal Precision Therapy Approach

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