A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

Yan, Helen H.N.; Siu, Hoi Cheong; Law, Simon; Ho, Simon S. M.; Yue, Sarah S K; Tsui, Wai Yin; Chan, Dessy; Chan, Alexander C.L.; Ma, Stephanie; Lam, Ka On; Bartfeld, Sina; Man, Alice H Y; Lee, Bernard C H; Chan, Acy; Wong, Jason; Cheng, S. W. Priscilla; Chan, Anthony K W; Zhang, Jiangwen; Shi, Jue; Fan, Xiaodan; Kwong, Dora Lai-Wan; Mak, Tak W.; Yuen, Siu Tsan; Clevers, Hans; Leung, Suet Yi

doi:10.1016/j.stem.2018.09.016

Cited by 507 publications

(554 citation statements)

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“…(Toolan, ; Taetle et al , ; Fu et al , ; Beckhove et al , ; Fichtner et al , ; Shultz et al , ; Wang et al , ; Cutz et al , ; Sato et al , , ; Hennessey et al , ; Gao et al , ; Karthaus et al , ; Boj et al , ; Lee et al , ; Li et al , , ; Sachs et al , ; Yan et al , ; Kopper et al , ; Schutgens et al , ).…”

Section: Introductionunclassified

“…Human tumour organoids have been generated from colon (Sato et al , ; van de Wetering et al , ), pancreas (Boj et al , ; Huang et al , ), prostate (Gao et al , ; Drost et al , ), breast (Sachs et al , ), gastric (Nanki et al , ; Yan et al , ), lung (Sachs et al , ), oesophageal (Li et al , ), bladder (Lee et al , ; Mullenders et al , ), ovarian (Kopper et al , ), kidney (Schutgens et al , ) and liver (Broutier et al , ; Li et al , ) tumour tissue (Fig ). An important feature of a number of these PDTOs is that they genetically and phenotypically mirror the tumour epithelium, including its intra‐tumour heterogeneity (Huang et al , ; van de Wetering et al , ; Nanki et al , ; Sachs et al , ; Yan et al , ). In a recent study, Roerink and colleagues characterized organoids derived from single cells from several colorectal cancers (CRC) and showed extensive mutational diversification as well as differences in responses to anti‐cancer drugs between even closely related cells of the same tumour (Roerink et al , ).…”

Section: Introductionmentioning

confidence: 99%

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Xenograft and organoid model systems in cancer research

et al. 2019

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Patient‐derived tumour xenografts and tumour organoids have become important preclinical model systems for cancer research. Both models maintain key features from their parental tumours, such as genetic and phenotypic heterogeneity, which allows them to be used for a wide spectrum of applications. In contrast to patient‐derived xenografts, organoids can be established and expanded with high efficiency from primary patient material. On the other hand, xenografts retain tumour–stroma interactions, which are known to contribute to tumorigenesis. In this review, we discuss recent advances in patient‐derived tumour xenograft and tumour organoid model systems and compare their promises and challenges as preclinical models in cancer research.

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Section: Introductionunclassified

Section: Introductionmentioning

confidence: 99%

Xenograft and organoid model systems in cancer research

et al. 2019

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“…A comparison of paired FGFR2 expression at baseline and 15 days post‐treatment further showed significant decreases in FGFR2 mRNA only in the sub‐clonal, heterogeneously amplified tumor, possibly reflecting clonal selection of non‐amplified compartments as a result of therapeutic pressure. In line with such observations, Yan and colleagues recently showed differential drug responses to PARP inhibition in two GC organoids derived from the same patient, with one organoid harboring a BRCA2 mutation exhibiting greater sensitivity …”

Section: Confounding Layers Of Complexities Underlie Gc Classificationmentioning

confidence: 65%

“…Previously discussed molecular classifications also hold implications for targeted therapies, exposing potential vulnerabilities such as PI3K/AKT/mTOR inhibitors in the Lei et al mesenchymal subtype, insulin‐like growth factor 1/insulin‐like growth factor 1 receptor (IGF1/IGF1R) inhibitors in the Oh et al MP subtype and nicotinamide phosphoribosyltransferase (NAMPT) inhibitors in the ACRG EMT subtype . These findings, subject to further validation, are especially exciting for the future of precision oncology, given the significant progress made recently in the development of patient‐derived organoids as drug‐testing platforms, which have shown the potential to recapitulate and predict in vivo patient clinical responses …”

Section: From Bench To Bedside: Translational and Clinical Utility Ofmentioning

confidence: 99%

“…52 These findings, subject to further validation, are especially exciting for the future of precision oncology, given the significant progress made recently in the development of patient-derived organoids as drug-testing platforms, which have shown the potential to recapitulate and predict in vivo patient clinical responses. 53,54 Converging evidence appears to suggest the presence of "immunogenic" tumor subtypes which benefit most from immunotherapy.…”

Section: From B En Ch To B Eds Ide: Tr An S L Ati Onal and Clini Cmentioning

confidence: 99%

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Dissection of gastric cancer heterogeneity for precision oncology

Tan

2019

Cancer Science

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Gastric cancer (GC) remains the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. Comprehensive ‐omic studies have unveiled a heterogeneous GC landscape, with considerable molecular diversity both between and within tumors. Given the complex nature of GC, a long‐sought goal includes effective identification of distinct patient subsets with prognostic and/or predictive outcomes to enable tailoring of specific treatments (“precision oncology”). In this review, we highlight various approaches to molecular classification in GC, covering recent genomic, transcriptomic, proteomic and epigenomic features. We pay special attention to the translational significance of classifier systems and examine potential confounding factors which deserve further investigation. In particular, we discuss recent advancements in our knowledge of intra‐subtype, intra‐patient and intra‐tumor heterogeneity, and the pivotal role of the tumor stromal microenvironment.

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Patient‐derived organoids as a preclinical platform for precision medicine in colorectal cancer

et al. 2022

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Patient‐derived organoids are being considered as models that can help guide personalized therapy through in vitro anticancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole‐exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an ‘organoid score’ based on the variable anticancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard‐of‐care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression‐free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA‐approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anticancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.

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A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

Cited by 507 publications

References 48 publications

Xenograft and organoid model systems in cancer research

Xenograft and organoid model systems in cancer research

Dissection of gastric cancer heterogeneity for precision oncology

Patient‐derived organoids as a preclinical platform for precision medicine in colorectal cancer

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