A subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors

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dc.contributor.authorH Fukamachi-
dc.contributor.authorSeon-Kyu Kim-
dc.contributor.authorJ Koh-
dc.contributor.authorH S Lee-
dc.contributor.authorY Sasaki-
dc.contributor.authorK Yamashita-
dc.contributor.authorT Nishikawaji-
dc.contributor.authorS Shimada-
dc.contributor.authorY Akiyama-
dc.contributor.authorS J Byeon-
dc.contributor.authorDong Hyuck Bae-
dc.contributor.authorK Okuno-
dc.contributor.authorM Nakagawa-
dc.contributor.authorT Tanioka-
dc.contributor.authorM Inokuchi-
dc.contributor.authorH Kawachi-
dc.contributor.authorK Tsuchiya-
dc.contributor.authorK Kojima-
dc.contributor.authorT Tokino-
dc.contributor.authorY Eishi-
dc.contributor.authorYong Sung Kim-
dc.contributor.authorW H Kim-
dc.contributor.authorY Yuasa-
dc.contributor.authorS Tanaka-
dc.date.accessioned2019-04-09T16:30:29Z-
dc.date.available2019-04-09T16:30:29Z-
dc.date.issued2019-
dc.identifier.issn17569966-
dc.identifier.uri10.1186/s13046-019-1121-3ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/18488-
dc.description.abstractBACKGROUND: Mechanistic target of rapamycin (mTOR) pathway is essential for the growth of gastric cancer (GC), but mTOR inhibitor everolimus was not effective for the treatment of GCs. The Cancer Genome Atlas (TCGA) researchers reported that most diffuse-type GCs were genomically stable (GS). Pathological analysis suggested that some diffuse-type GCs developed from intestinal-type GCs. METHODS: We established patient-derived xenograft (PDX) lines from diffuse-type GCs, and searched for drugs that suppressed their growth. Diffuse-type GCs were classified into subtypes by their gene expression profiles. RESULTS: mTOR inhibitor temsirolimus strongly suppressed the growth of PDX-derived diffuse-type GC-initiating cells, which was regulated via Wnt-mTOR axis. These cells were microsatellite unstable (MSI) or chromosomally unstable (CIN), inconsistent with TCGA report. Diffuse-type GCs in TCGA cohort could be classified into two clusters, and GS subtype was major in cluster I while CIN and MSI subtypes were predominant in cluster II where PDX-derived diffuse-type GC cells were included. We estimated that about 9 and 55% of the diffuse-type GCs in cluster II were responders to mTOR inhibitors and checkpoint inhibitors, respectively, by identifying PIK3CA mutations and MSI condition in TCGA cohort. These ratios were far greater than those of diffuse-type GCs in cluster I or intestinal-type GCs. Further analysis suggested that diffuse-type GCs in cluster II developed from intestinal-type GCs while those in cluster I from normal gastric epithelial cells. CONCLUSION: mTOR inhibitors and checkpoint inhibitors might be useful for the treatment of a subset of diffuse-type GCs which may develop from intestinal-type GCs.-
dc.publisherSpringer-BMC-
dc.titleA subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors-
dc.title.alternativeA subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors-
dc.typeArticle-
dc.citation.titleJournal of Experimental & Clinical Cancer Research-
dc.citation.number0-
dc.citation.endPage127-
dc.citation.startPage127-
dc.citation.volume38-
dc.contributor.affiliatedAuthorSeon-Kyu Kim-
dc.contributor.affiliatedAuthorDong Hyuck Bae-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeNameFukamachi-
dc.contributor.alternativeName김선규-
dc.contributor.alternativeName고지원-
dc.contributor.alternativeName이혜승-
dc.contributor.alternativeNameSasaki-
dc.contributor.alternativeNameYamashita-
dc.contributor.alternativeNameNishikawaji-
dc.contributor.alternativeNameShimada-
dc.contributor.alternativeNameAkiyama-
dc.contributor.alternativeName변선주-
dc.contributor.alternativeName배동혁-
dc.contributor.alternativeNameOkuno-
dc.contributor.alternativeNameNakagawa-
dc.contributor.alternativeNameTanioka-
dc.contributor.alternativeNameInokuchi-
dc.contributor.alternativeNameKawachi-
dc.contributor.alternativeNameTsuchiya-
dc.contributor.alternativeNameKojima-
dc.contributor.alternativeNameTokino-
dc.contributor.alternativeNameEishi-
dc.contributor.alternativeName김용성-
dc.contributor.alternativeName김우호-
dc.contributor.alternativeNameYuasa-
dc.contributor.alternativeNameTanaka-
dc.identifier.bibliographicCitationJournal of Experimental & Clinical Cancer Research, vol. 38, pp. 127-127-
dc.identifier.doi10.1186/s13046-019-1121-3-
dc.subject.keywordDiffuse-type gastric cancer-
dc.subject.keywordImmune checkpoint inhibitor-
dc.subject.keywordMicrosatellite unstable-
dc.subject.keywordPD-L1-
dc.subject.keywordPIK3CA-
dc.subject.keywordPatient-derived xenograft-
dc.subject.keywordPrimary culture-
dc.subject.keywordTemsirolimus-
dc.subject.keywordmTOR inhibitor-
dc.subject.localDiffuse-type gastric cancer-
dc.subject.localImmune checkpoint inhibitor-
dc.subject.localMicrosatellite unstable-
dc.subject.localPD-L1-
dc.subject.localPIK3CA-
dc.subject.localPatient-derived xenograft-
dc.subject.localPrimary culture-
dc.subject.localTemsirolimus-
dc.subject.localmTOR inhibitor-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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