The Use of Endometrial Cancer Patient–Derived Organoid Culture for Drug Sensitivity Testing Is Feasible

Girda, Eugenia; Huang, Eric C.; Leiserowitz, Gary S.; Smith, Lloyd H.

doi:10.1097/igc.0000000000001061

Cited by 55 publications

(54 citation statements)

References 17 publications

(22 reference statements)

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“…In addition to benign endometrial organoid models, organoids have also been derived from endometrial cancer tissues, and used for drug testing. [65][66][67][68] These endometrial cancer organoids recapitulated genetic and phenotypic characteristics of endometrial tumors, and could be an efficient way of testing therapies. [66][67][68] Organoids have also been derived from the endometrium of patients with other diseases, including endometrial hyperplasia, Lynch syndrome, and endometriosis.…”

Section: Human Endometrial Organoids: Recapitulating Native Tissues Wmentioning

confidence: 99%

“…[65][66][67][68] These endometrial cancer organoids recapitulated genetic and phenotypic characteristics of endometrial tumors, and could be an efficient way of testing therapies. [66][67][68] Organoids have also been derived from the endometrium of patients with other diseases, including endometrial hyperplasia, Lynch syndrome, and endometriosis. 65 Endometrial organoids have provided an alternate physiologic model of the endometrium that can be adapted to biobanking, drug screenings, and investigation of endometrial physiology and pathology.…”

Section: Human Endometrial Organoids: Recapitulating Native Tissues Wmentioning

confidence: 99%

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Microphysiological Modeling of the Human Endometrium

Campo

Murphy

Yıldız

et al. 2020

Tissue Engineering Part A

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Since the beginning of clinical medicine, the human uterus has held the fascination of clinicians and researchers, given its critical role in the reproduction of our species. The endometrial lining provides residence for the embryo; however, this symbiotic interaction can be disrupted if the timing is not correct and the endometrium is not receptive. Diseases associated with the endometrium interfere with the reproductive process and cause a life-altering burden of pain and even death. With the advancement of technologies and new insights into the biology of the endometrium, much has been uncovered about the dynamic and essential changes that need to occur for normal endometrial function, as well as aberrations that lead to endometrial diseases. As expected, the more that is uncovered, the more the complexity of the endometrium is made evident. In this study, we bring together three areas of scientific advancement that remain in their infancy, but which together have the potential to mirror this complexity and enable understanding. Studies on induced pluripotent stem cells, threedimensional tissue mimics, and microfluidic culture platforms will be reviewed with a focus on the endometrium. These unconventional approaches will provide new perspectives and appreciation for the elegance and complexity of the endometrium.

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Section: Human Endometrial Organoids: Recapitulating Native Tissues Wmentioning

confidence: 99%

Section: Human Endometrial Organoids: Recapitulating Native Tissues Wmentioning

confidence: 99%

Microphysiological Modeling of the Human Endometrium

Campo

Murphy

Yıldız

et al. 2020

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…Girda et al generated 15 organoids from 14 endometrial and 1 metastatic tumors. The organoids had similar morphological features to their parental tumors.…”

Section: Pdtos As Potential Tumor Models For Drug Screening and Drug mentioning

confidence: 99%

The promises and challenges of patient‐derived tumor organoids in drug development and precision oncology

Granat

Kambhampati

Klosek

et al. 2019

Anim Models and Exp Med

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In the era of precision medicine, cancer researchers and oncologists are eagerly searching for more realistic, cost effective, and timely tumor models to aid drug development and precision oncology. Tumor models that can faithfully recapitulate the histological and molecular characteristics of various human tumors will be extremely valuable in increasing the successful rate of oncology drug development and discovering the most efficacious treatment regimen for cancer patients. Two-dimensional (2D) cultured cancer cell lines, genetically engineered mouse tumor (GEMT) models, and patient-derived tumor xenograft (PDTX) models have been widely used to investigate the biology of various types of cancers and test the efficacy of oncology drug candidates. However, due to either the failure to faithfully recapitulate the complexity of patient tumors in the case of 2D cultured cancer cells, or high cost and untimely for drug screening and testing in the case of GEMT and PDTX, new tumor models are urgently needed. The recently developed patient-derived tumor organoids (PDTO) offer great potentials in uncovering novel biology of cancer development, accelerating the discovery of oncology drugs, and individualizing the treatment of cancers.In this review, we will summarize the recent progress in utilizing PDTO for oncology drug discovery. In addition, we will discuss the potentials and limitations of the current PDTO tumor models. K E Y W O R D S drug testing, patient derived tumor organoids, precision oncology, tumor models | 151 GRANAT eT Al. not be present in cells when grown in vivo. 4 Third, the growth medium used for culturing cancer cell lines is not able to completely mirror the conditions and environment that tumor cells naturally reside in. In vivo, tumor cells are surrounded by fibroblasts, blood vessels, and immune cells, and their collective interactions are important; this aspect is unfortunately missing in the cultured cancer cell lines. 5 Therefore, the in vitro cultured 2D cancer cell lines are the least faithful tumor model to be able to recapitulate patient tumors. By growing the established cancer cell lines in a three-dimensional (3D) environment, which mimics the in vivo extracellular matrix, the so called 3D cell culture moves a step closer to the in vivo tumors. 6However, the 3D cell culture still lacks the complex tissue hierarchy comparing to the primary tumors. 6 Therefore, the 3D cell culture is not ideal for investigating the tumor biology and testing oncology drugs. | Genetically engineered mouse tumor modelsDue to the aforementioned limitations, another commonly utilized model in cancer research is the genetically engineered mouse tumor (GEMT) model. In contrast to transplanting cancer cell lines into mice, which requires an immunocompromised status of the host mice to prevent rejection, GEMT is immunocompetent. 7 Therefore, GEMT can be potentially used for the investigation of immunotherapy. However, mouse tumor models often do not faithfully recapitulate the human cancers. Furthermore, generat...

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“…Therefore, since cost-effective techniques are required, in vitro systems, including patient-derived tumor organoid (PDO) or spheroid models that accurately recapitulate tissue architecture and function, have been developed recently. The establishment of human tumor organoids has been recently reported for colon ( 12 – 14 ), pancreatic ( 15 ), prostate ( 16 ), endometrial ( 17 ), and liver ( 18 ) tumors, among others. In particular, Pauli et al ( 19 ) reported 56 PDOs that were established from bladder, breast, brain, colon, lung, kidney, ovarian, pancreatic, prostate, stomach and uterine cancers, among others, in addition to the development of high-throughput screening (HTS) using these systems.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues

et al. 2018

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Patient-derived tumor xenograft models represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture; however, their use is low-throughput and costly. To overcome this limitation, patient-derived tumor organoids (PDOs) were established from human lung, ovarian and uterine tumor tissues, among others, to accurately and efficiently recapitulate the tissue architecture and function. PDOs were able to be cultured for >6 months, and formed cell clusters with similar morphologies to their source tumors. Comparative histological and comprehensive gene expression analyses proved that the characteristics of PDOs were similar to those of their source tumors, even following long-term expansion in culture. At present, 53 PDOs have been established by the Fukushima Translational Research Project, and were designated as Fukushima PDOs (F-PDOs). In addition, the in vivo tumorigenesis of certain F-PDOs was confirmed using a xenograft model. The present study represents a detailed analysis of three F-PDOs (termed REME9, 11 and 16) established from endometrial cancer tissues. These were used for cell growth inhibition experiments using anticancer agents. A suitable high-throughput assay system, with 96- or 384-well plates, was designed for each F-PDO, and the efficacy of the anticancer agents was subsequently evaluated. REME9 and 11 exhibited distinct responses and increased resistance to the drugs, as compared with conventional cancer cell lines (AN3 CA and RL95-2). REME9 and 11, which were established from tumors that originated in patients who did not respond to paclitaxel and carboplatin (the standard chemotherapy for endometrial cancer), exhibited high resistance (half-maximal inhibitory concentration >10 µM) to the two agents. Therefore, assay systems using F-PDOs may be utilized to evaluate anticancer agents using conditions that better reflect clinical conditions, compared with conventional methods using cancer cell lines, and to discover markers that identify the pharmacological effects of anticancer agents.

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The Use of Endometrial Cancer Patient–Derived Organoid Culture for Drug Sensitivity Testing Is Feasible

Abstract: Supplemental digital content is available in the text.

Cited by 55 publications

References 17 publications

Microphysiological Modeling of the Human Endometrium

Microphysiological Modeling of the Human Endometrium

The promises and challenges of patient‐derived tumor organoids in drug development and precision oncology

Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues

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