Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing
Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibitin...
Ausführliche Beschreibung
Autor*in: |
Ming Zu [verfasserIn] Xinyu Hao [verfasserIn] Jing Ning [verfasserIn] Xin Zhou [verfasserIn] Yueqing Gong [verfasserIn] Yanfei Lang [verfasserIn] Weichao Xu [verfasserIn] Jing Zhang [verfasserIn] Shigang Ding [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2023 |
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Übergeordnetes Werk: |
In: Biomedicine & Pharmacotherapy - Elsevier, 2021, 163(2023), Seite 114751- |
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Übergeordnetes Werk: |
volume:163 ; year:2023 ; pages:114751- |
Links: |
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DOI / URN: |
10.1016/j.biopha.2023.114751 |
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Katalog-ID: |
DOAJ089934504 |
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520 | |a Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. | ||
650 | 4 | |a Gastric cancer | |
650 | 4 | |a Patient-derived organoids (PDOs) | |
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10.1016/j.biopha.2023.114751 doi (DE-627)DOAJ089934504 (DE-599)DOAJb2c444f010a4408aa3d3d1e4a15781e0 DE-627 ger DE-627 rakwb eng RM1-950 Ming Zu verfasserin aut Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. Gastric cancer Patient-derived organoids (PDOs) Drug sensitivity test Personalized medicine Therapeutics. Pharmacology Xinyu Hao verfasserin aut Jing Ning verfasserin aut Xin Zhou verfasserin aut Yueqing Gong verfasserin aut Yanfei Lang verfasserin aut Weichao Xu verfasserin aut Jing Zhang verfasserin aut Shigang Ding verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 163(2023), Seite 114751- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:163 year:2023 pages:114751- https://doi.org/10.1016/j.biopha.2023.114751 kostenfrei https://doaj.org/article/b2c444f010a4408aa3d3d1e4a15781e0 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223005401 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 163 2023 114751- |
spelling |
10.1016/j.biopha.2023.114751 doi (DE-627)DOAJ089934504 (DE-599)DOAJb2c444f010a4408aa3d3d1e4a15781e0 DE-627 ger DE-627 rakwb eng RM1-950 Ming Zu verfasserin aut Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. Gastric cancer Patient-derived organoids (PDOs) Drug sensitivity test Personalized medicine Therapeutics. Pharmacology Xinyu Hao verfasserin aut Jing Ning verfasserin aut Xin Zhou verfasserin aut Yueqing Gong verfasserin aut Yanfei Lang verfasserin aut Weichao Xu verfasserin aut Jing Zhang verfasserin aut Shigang Ding verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 163(2023), Seite 114751- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:163 year:2023 pages:114751- https://doi.org/10.1016/j.biopha.2023.114751 kostenfrei https://doaj.org/article/b2c444f010a4408aa3d3d1e4a15781e0 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223005401 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 163 2023 114751- |
allfields_unstemmed |
10.1016/j.biopha.2023.114751 doi (DE-627)DOAJ089934504 (DE-599)DOAJb2c444f010a4408aa3d3d1e4a15781e0 DE-627 ger DE-627 rakwb eng RM1-950 Ming Zu verfasserin aut Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. Gastric cancer Patient-derived organoids (PDOs) Drug sensitivity test Personalized medicine Therapeutics. Pharmacology Xinyu Hao verfasserin aut Jing Ning verfasserin aut Xin Zhou verfasserin aut Yueqing Gong verfasserin aut Yanfei Lang verfasserin aut Weichao Xu verfasserin aut Jing Zhang verfasserin aut Shigang Ding verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 163(2023), Seite 114751- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:163 year:2023 pages:114751- https://doi.org/10.1016/j.biopha.2023.114751 kostenfrei https://doaj.org/article/b2c444f010a4408aa3d3d1e4a15781e0 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223005401 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 163 2023 114751- |
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10.1016/j.biopha.2023.114751 doi (DE-627)DOAJ089934504 (DE-599)DOAJb2c444f010a4408aa3d3d1e4a15781e0 DE-627 ger DE-627 rakwb eng RM1-950 Ming Zu verfasserin aut Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. Gastric cancer Patient-derived organoids (PDOs) Drug sensitivity test Personalized medicine Therapeutics. Pharmacology Xinyu Hao verfasserin aut Jing Ning verfasserin aut Xin Zhou verfasserin aut Yueqing Gong verfasserin aut Yanfei Lang verfasserin aut Weichao Xu verfasserin aut Jing Zhang verfasserin aut Shigang Ding verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 163(2023), Seite 114751- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:163 year:2023 pages:114751- https://doi.org/10.1016/j.biopha.2023.114751 kostenfrei https://doaj.org/article/b2c444f010a4408aa3d3d1e4a15781e0 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223005401 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 163 2023 114751- |
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10.1016/j.biopha.2023.114751 doi (DE-627)DOAJ089934504 (DE-599)DOAJb2c444f010a4408aa3d3d1e4a15781e0 DE-627 ger DE-627 rakwb eng RM1-950 Ming Zu verfasserin aut Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. Gastric cancer Patient-derived organoids (PDOs) Drug sensitivity test Personalized medicine Therapeutics. Pharmacology Xinyu Hao verfasserin aut Jing Ning verfasserin aut Xin Zhou verfasserin aut Yueqing Gong verfasserin aut Yanfei Lang verfasserin aut Weichao Xu verfasserin aut Jing Zhang verfasserin aut Shigang Ding verfasserin aut In Biomedicine & Pharmacotherapy Elsevier, 2021 163(2023), Seite 114751- (DE-627)306717565 (DE-600)1501510-5 19506007 nnns volume:163 year:2023 pages:114751- https://doi.org/10.1016/j.biopha.2023.114751 kostenfrei https://doaj.org/article/b2c444f010a4408aa3d3d1e4a15781e0 kostenfrei http://www.sciencedirect.com/science/article/pii/S0753332223005401 kostenfrei https://doaj.org/toc/0753-3322 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 163 2023 114751- |
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patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing |
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Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing |
abstract |
Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. |
abstractGer |
Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. |
abstract_unstemmed |
Background: Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine. Methods: PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data. Results: Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient. Conclusions: PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment. |
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title_short |
Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing |
url |
https://doi.org/10.1016/j.biopha.2023.114751 https://doaj.org/article/b2c444f010a4408aa3d3d1e4a15781e0 http://www.sciencedirect.com/science/article/pii/S0753332223005401 https://doaj.org/toc/0753-3322 |
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Xinyu Hao Jing Ning Xin Zhou Yueqing Gong Yanfei Lang Weichao Xu Jing Zhang Shigang Ding |
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