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Conference Paper: Establishment of human primary hepatocellular carcinoma-derived organoid cultures for disease modeling and drug screening

TitleEstablishment of human primary hepatocellular carcinoma-derived organoid cultures for disease modeling and drug screening
Authors
Issue Date2018
PublisherInternational Society for Stem Cell Research.
Citation
International Society for Stem Cell Research (ISSCR) Annual Meeting, Melbourne, Australia, 20-23 June 2018 How to Cite?
AbstractHepatocellular carcinoma (HCC) is a leading cause of cancer fatalities globally, with a particularly high prevalence in Southeast Asia and Hong Kong. Recent next generation sequencing studies revealed that a majority of HCC harbors recurrent mutations, many of which are targets of current approved drugs. However, further translational research of these findings into novel HCC therapies has been precluded by the lack of reliable experimental models. The value of 2-dimensional (2D) cancer cell culture in predicting clinical efficacy has been continuously challenged, while the establishment rates of patient-derived xenografts (PDX) are low, time-consuming and even if successful, limited by their scalability. Recent reports have found liver cancerderived 3-dimensional (3D) organoid cultures to highly recapitulate features of the most common subtypes of human primary liver tumors. Based on this protocol, we have successfully established a pilot bio-bank of HCC organoids specific to Asian ethnicity. Our HCC organoids fully resemble histological architecture of their corresponding original tumor tissue, with HCC phenotype validated by the presence of both hepatocellular markers AFP and GPC3, as well as the absence of ductal/cholangiocarcinoma markers CK19 and EpCAM. Whole exome sequencing revealed that these HCC organoids and their corresponding tumor tissues concordantly harbor driver mutations in tumor suppressor genes including the more frequently mutated TSC2 and AXIN1, which have both previously been documented in large-scale HCC studies. In addition, our HCC organoid samples also retain the hepatitis B virus (HBV) genome, closely mimicking one of the common features of Asian HCC. The successful establishment of these patient-derived HCC organoids will allow for a wide spectrum of biological processes including drug sensitivity screening as well as disease modeling. Applications of these new pre-clinical HCC models will shed insight into drug resistance mechanisms of HCC and facilitate the development and translation of HCC targeted therapies.
DescriptionPoster abstract - Session: Organoids - no. W-2086
Persistent Identifierhttp://hdl.handle.net/10722/256237

 

DC FieldValueLanguage
dc.contributor.authorZhou, L-
dc.contributor.authorSiu, HC-
dc.contributor.authorTong, M-
dc.contributor.authorChai, S-
dc.contributor.authorLoong, HC-
dc.contributor.authorSin, S-
dc.contributor.authorClevers, H-
dc.contributor.authorLo, CM-
dc.contributor.authorMan, K-
dc.contributor.authorGuan, X-
dc.contributor.authorWong, D-
dc.contributor.authorYan, HHN-
dc.contributor.authorLeung, SY-
dc.contributor.authorMa, SKY-
dc.date.accessioned2018-07-20T06:31:28Z-
dc.date.available2018-07-20T06:31:28Z-
dc.date.issued2018-
dc.identifier.citationInternational Society for Stem Cell Research (ISSCR) Annual Meeting, Melbourne, Australia, 20-23 June 2018-
dc.identifier.urihttp://hdl.handle.net/10722/256237-
dc.descriptionPoster abstract - Session: Organoids - no. W-2086-
dc.description.abstractHepatocellular carcinoma (HCC) is a leading cause of cancer fatalities globally, with a particularly high prevalence in Southeast Asia and Hong Kong. Recent next generation sequencing studies revealed that a majority of HCC harbors recurrent mutations, many of which are targets of current approved drugs. However, further translational research of these findings into novel HCC therapies has been precluded by the lack of reliable experimental models. The value of 2-dimensional (2D) cancer cell culture in predicting clinical efficacy has been continuously challenged, while the establishment rates of patient-derived xenografts (PDX) are low, time-consuming and even if successful, limited by their scalability. Recent reports have found liver cancerderived 3-dimensional (3D) organoid cultures to highly recapitulate features of the most common subtypes of human primary liver tumors. Based on this protocol, we have successfully established a pilot bio-bank of HCC organoids specific to Asian ethnicity. Our HCC organoids fully resemble histological architecture of their corresponding original tumor tissue, with HCC phenotype validated by the presence of both hepatocellular markers AFP and GPC3, as well as the absence of ductal/cholangiocarcinoma markers CK19 and EpCAM. Whole exome sequencing revealed that these HCC organoids and their corresponding tumor tissues concordantly harbor driver mutations in tumor suppressor genes including the more frequently mutated TSC2 and AXIN1, which have both previously been documented in large-scale HCC studies. In addition, our HCC organoid samples also retain the hepatitis B virus (HBV) genome, closely mimicking one of the common features of Asian HCC. The successful establishment of these patient-derived HCC organoids will allow for a wide spectrum of biological processes including drug sensitivity screening as well as disease modeling. Applications of these new pre-clinical HCC models will shed insight into drug resistance mechanisms of HCC and facilitate the development and translation of HCC targeted therapies.-
dc.languageeng-
dc.publisherInternational Society for Stem Cell Research.-
dc.relation.ispartofInternational Society for Stem Cell Research (ISSCR) Annual Meeting-
dc.titleEstablishment of human primary hepatocellular carcinoma-derived organoid cultures for disease modeling and drug screening-
dc.typeConference_Paper-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.emailLeung, SY: suetyi@hku.hk-
dc.identifier.emailMa, SKY: stefma@hku.hk-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.authorityLeung, SY=rp00359-
dc.identifier.authorityMa, SKY=rp00506-
dc.identifier.hkuros286386-
dc.identifier.hkuros290365-
dc.publisher.placeUnited States-

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