2024
1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial
Sachdeva M, Tay R, KIM Y, Kim H, Cheong J, Grabsch H, Sundar R. 1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial. Annals Of Oncology 2024, 35: s885. DOI: 10.1016/j.annonc.2024.08.1484.Peer-Reviewed Original ResearchSpatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases
Zhao J, Ong C, Srivastava S, Chia D, Ma H, Huang K, Sheng T, Ramnarayanan K, Ong X, Tay S, Hagihara T, Tan A, Teo M, Tan Q, Ng G, Tan J, Ng M, Gwee Y, Walsh R, Law J, Shabbir A, Kim G, Tay Y, Her Z, Leoncini G, Teh B, Hong J, Tay R, Teo C, Dings M, Bijlsma M, Lum J, Mathur S, Pietrantonio F, Blum S, van Laarhoven H, Klempner S, Yong W, So J, Chen Q, Tan P, Sundar R. Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases. Gastroenterology 2024 PMID: 39147169, DOI: 10.1053/j.gastro.2024.08.007.Peer-Reviewed Original ResearchPeritoneal metastasisTumor microenvironmentPrimary tumorTranscoelomic metastasisGastric cancerExpression of therapeutic targetsAssociated with poor prognosisGastric cancer peritoneal metastasisAssociated with increased riskHumanized mouse modelTherapeutic targetComprehensive multi-omics analysisTumor microenvironment signaturesTumor microenvironment alterationsDigital spatial profilingInvestigate molecular alterationsWhole-exome sequencingMatched normal tissuesStromal infiltrationComprehensive molecular characterizationLiver metastasesImmune compositionFGFR2b expressionImprove patient outcomesPredictive markerAbstract P28: Comprehensive Molecular Phenotyping of ARID1A -deficient Gastric Cancer Reveals Pervasive Epigenomic Reprogramming and Therapeutic Opportunities
Xu C, Huang K, Law J, Chua J, Sheng T, Flores N, Pizzi M, Okabe A, Tan A, Zhu F, Kumar V, Lu X, Benitez A, Lian B, Ma H, Ho S, Ramnarayanan K, Anene-Nzelu C, Razavi-Mohseni M, Ghani S, Tay S, Ong X, Lee M, Guo Y, Ashktorab H, Smoot D, Li S, Skanderup A, Beer M, Foo R, Wong J, Sanghvi K, Yong W, Sundar R, Kaneda A, Prabhakar S, Mazur P, Ajani J, Yeoh K, So J, Tan P. Abstract P28: Comprehensive Molecular Phenotyping of ARID1A -deficient Gastric Cancer Reveals Pervasive Epigenomic Reprogramming and Therapeutic Opportunities. Cancer Research 2024, 84: p28-p28. DOI: 10.1158/1538-7445.fcs2023-p28.Peer-Reviewed Original ResearchGastric cancerMolecular subtypesARID1A lossPro-inflammatory tumor microenvironmentTherapeutic opportunitiesARID1A inactivationTumor microenvironmental changesEpigenomic reprogrammingMutational signaturesPromoter activityGastric cell linesARID1A depletionTumor-intrinsicTumor inflammationTumor microenvironmentSingle-cell transcriptome profilingMutated driver genesTherapeutic vulnerabilitiesGC molecular subtypesNFkB inhibitorARID1ATherapeutic strategiesPharmacological inhibitionGC patientsSingapore cohortAbstract 1497: Humanized mouse model unveils niche conditioning in gastric cancer peritoneal metastasis
Zhao J, Chia D, Her Z, Ma H, Ong X, Tay S, So J, Chen Q, Tan P, Sundar R. Abstract 1497: Humanized mouse model unveils niche conditioning in gastric cancer peritoneal metastasis. Cancer Research 2024, 84: 1497-1497. DOI: 10.1158/1538-7445.am2024-1497.Peer-Reviewed Original ResearchHumanized mouse modelPeritoneal metastasisGastric cancer peritoneal metastasisPrimary tumorAdjacent peritoneumMouse modelTranscoelomic metastasisHost immune systemEpithelial mesenchymal transitionOrthotopic modelAmerican Association for Cancer Research annual meetingsGastric cancerNovel humanized mouse modelNSG modelImmune systemExpression of M2 macrophagesFunctional human cellsPeritoneal disseminationT-regsOrthotopic inoculationDendritic cellsNOD-SCIDImmune infiltrationPeritoneal samplesNormal peritoneumOncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis.
Zhao J, Huang K, Chia D, Law J, Tan A, So J, Tan P, Sundar R. Oncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis. Journal Of Clinical Oncology 2024, 42: 392-392. DOI: 10.1200/jco.2024.42.3_suppl.392.Peer-Reviewed Original ResearchPeritoneal metastasisPrimary tumorWhole-exome sequencingARID1A mutationsGastric cancerMedian follow-up durationGS tumorsPrimary tumors of patientsMetachronous peritoneal metastasesAssociated with PMFollow-up durationGastric cancer tumorsPoor survival outcomesPrimary GC tumorsMetachronous PMAdvanced tumorsCDH1 mutationsSurgical resectionOncogenic aberrationsSurvival outcomesClinical outcomesPoor prognosisFollowed-upProspective cohortRHOA mutations
2023
Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression
Huang K, Ma H, Chong R, Uchihara T, Lian B, Zhu F, Sheng T, Srivastava S, Tay S, Sundar R, Tan A, Ong X, Lee M, Ho S, Lesluyes T, Ashktorab H, Smoot D, Van Loo P, Chua J, Ramnarayanan K, Lau L, Gotoda T, Kim H, Ang T, Khor C, Lee J, Tsao S, Yang W, Teh M, Chung H, So J, Yeoh K, Tan P, Consortium S. Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression. Cancer Cell 2023, 41: 2019-2037.e8. PMID: 37890493, PMCID: PMC10729843, DOI: 10.1016/j.ccell.2023.10.004.Peer-Reviewed Original ResearchConceptsIntestinal metaplasiaProspective 10-year studyPre-malignant conditionChromatin regulationGastric cancer progressionMicrobial communitiesClinical-only modelClinical-genomic modelsCellular compartmentsIntestinal homeostasisMicrobial dysbiosisTranscriptome profilingDriver genesARID1A mutationsDiverse pathwaysIM patientsClonal dynamicsGenomic profilingSingle-cellEarly malignancyGC riskCell typesGastric cancerCancer progressionLineage heterogeneityPhase II study of trifluridine/tipiracil in metastatic breast cancers with or without prior exposure to fluoropyrimidines
Lim J, Ow S, Wong A, Lee M, Chan G, Low J, Sundar R, Choo J, Chong W, Ang Y, Tai B, Lee S. Phase II study of trifluridine/tipiracil in metastatic breast cancers with or without prior exposure to fluoropyrimidines. European Journal Of Cancer 2023, 193: 113311. PMID: 37717281, DOI: 10.1016/j.ejca.2023.113311.Peer-Reviewed Original ResearchMetastatic breast cancerObjective response rateProgression-free survivalPhase II studyCohort ABreast cancerDetermination of progression-free survivalSingle-arm phase II studyTreatment of metastatic breast cancerConsistent with known toxicitiesMedian progression-free survivalClinical benefit rateDose-confirmation phaseTreated with FTD/TPIDose modificationII studyCohort BBenefit rateFTD/TPISafety profileFluoropyrimidineGastric cancerPatientsResponse rateAntitumour activityComprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities
Xu C, Huang K, Law J, Chua J, Sheng T, Flores N, Pizzi M, Okabe A, Tan A, Zhu F, Kumar V, Lu X, Benitez A, Lian B, Ma H, Ho S, Ramnarayanan K, Anene-Nzelu C, Razavi-Mohseni M, Ghani S, Tay S, Ong X, Lee M, Guo Y, Ashktorab H, Smoot D, Li S, Skanderup A, Beer M, Foo R, Wong J, Sanghvi K, Yong W, Sundar R, Kaneda A, Prabhakar S, Mazur P, Ajani J, Yeoh K, So J, Tan P. Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities. Gut 2023, 72: 1651-1663. PMID: 36918265, DOI: 10.1136/gutjnl-2022-328332.Peer-Reviewed Original ResearchConceptsGastric cancerMolecular subtypesPromoter activityMutational signaturesProinflammatory tumor microenvironmentTumor microenvironmental changesMutated driver genesSingle-cell transcriptome profilingCTCF occupancyGC molecular subtypesChromatin profilingDistal enhancerRegulatory networksEpigenetic landscapeBRD4 bindingEpigenomic reprogrammingEpigenomic levelsTumor-intrinsicTumor inflammationTumor microenvironmentTherapeutic vulnerabilitiesTranscriptome profilingDriver genesNFkB inhibitorGene expressionClinical relevance of PD-1 positive CD8 T-cells in gastric cancer
Choo J, Kua L, Soe M, Asuncion B, Tan B, Teo C, Tay R, So J, Shabbir A, Guowei K, Tan H, Chan G, Ma H, Ramachandran G, Lum J, Chee C, Sridharan S, Tan P, Sundar R, Yong W. Clinical relevance of PD-1 positive CD8 T-cells in gastric cancer. Gastric Cancer 2023, 26: 393-404. PMID: 36781556, PMCID: PMC10115710, DOI: 10.1007/s10120-023-01364-7.Peer-Reviewed Original ResearchConceptsCD8 T cellsPD-1+CD8+ T cellsT cellsTumor microenvironmentPD-1Overall survivalGastric cancerMultiplex immunohistochemistryT cell-inflamed tumor microenvironmentAssociated with improved OSIncreased PD-1 expressionClinical relevanceGranzyme-B expressionInflamed tumor microenvironmentPD-1 expressionInfluence overall survivalNK cell proportionTreated with immunotherapyPhase 2 trialAssociated with chemotherapyCox proportional hazards modelsProportional hazards modelImproved OSImmunotherapy sensitivityNK cellsMalignant ascites as a marker of peritoneal carcinomatosis burden in patients with colorectal and gastroesophageal cancer.
Gwee Y, Chia D, Provenzano L, Lonardi S, Conca V, Cremolini C, Yong W, Tan P, So J, Kim G, Shabbir A, Ong J, Pietrantonio F, Sundar R. Malignant ascites as a marker of peritoneal carcinomatosis burden in patients with colorectal and gastroesophageal cancer. Journal Of Clinical Oncology 2023, 41: 455-455. DOI: 10.1200/jco.2023.41.4_suppl.455.Peer-Reviewed Original ResearchPeritoneal cancer indexPresence of malignant ascitesPeritoneal metastasisMalignant ascitesColorectal cancer patientsGastric cancerColorectal cancerOverall survivalGastrointestinal malignanciesPoor survivalCohort of gastric cancerMedian peritoneal cancer indexPeritoneal cancer index scoreFirst-line systemic treatmentResistant to systemic therapyMetastatic gastrointestinal malignanciesMedian overall survivalStage IV diseaseMetastatic CRC patientsAbsence of ascitesClinico-pathological dataPoor survival outcomesTertiary oncology centerStudy of patientsRandomized clinical trials
2022
Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 30: 1889-1890. PMID: 36564654, DOI: 10.1245/s10434-022-12877-3.Peer-Reviewed Original ResearchASO Visual Abstract: Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Goh G, Seet J, Chee C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Teh J, Lwin A, Soon Y, Shabbir A, So J, Yong W. ASO Visual Abstract: Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8608-8609. DOI: 10.1245/s10434-022-12043-9.Peer-Reviewed Original ResearchASO Author Reflections: Combination Intra-Peritoneal and Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastases
Chia D, Ang J, Sundar R, Kim G, Shabbir A, So J, Yong W. ASO Author Reflections: Combination Intra-Peritoneal and Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8606-8607. PMID: 36192514, DOI: 10.1245/s10434-022-12102-1.Peer-Reviewed Original ResearchRegulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities
Ho S, Sheng T, Xing M, Ooi W, Xu C, Sundar R, Huang K, Li Z, Kumar V, Ramnarayanan K, Zhu F, Srivastava S, Bin Adam Isa Z, Anene-Nzelu C, Razavi-Mohseni M, Shigaki D, Ma H, Tan A, Ong X, Lee M, Tay S, Guo Y, Huang W, Li S, Beer M, Foo R, Teh M, Skanderup A, Teh B, Tan P. Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities. Gut 2022, 72: 226-241. PMID: 35817555, DOI: 10.1136/gutjnl-2021-326483.Peer-Reviewed Original ResearchConceptsEpigenomic landscapeGastric cancerEnhancer landscapeGenome-wide epigenomic profilesDownstream targetsPharmacological inhibitionCell linesClinically aggressive subtypeTargetable genomic alterationsMultiple molecular subtypesChIP-seqPoor patient survivalGenomic associationsGC cell linesTranscriptomic scenarioEpigenomic profilingSuper-enhancersChromatin immunoprecipitationRNA sequencingTranscriptome profilingUpstream regulatorGenomic alterationsTherapy resistanceCRISPR/Cas9 editingPatient survivalChoice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy
Yeong J, Lum H, Teo C, Tan B, Chan Y, Tay R, Choo J, Jeyasekharan A, Miow Q, Loo L, Yong W, Sundar R. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Gastric Cancer 2022, 25: 741-750. PMID: 35661944, PMCID: PMC9226082, DOI: 10.1007/s10120-022-01301-0.Peer-Reviewed Original ResearchConceptsCombined positive scorePD-L1 combined positive scoreTumor proportion scorePD-L1Gastric cancerImmune cellsPD-L1 immunohistochemistry assaysProgrammed death-ligand 1Resection of gastric cancerStandard-of-care treatmentBackgroundImmune checkpoint inhibitorsGastric cancer immunotherapyPD-L1 positivityPD-L1 scoringPD-L1 immunohistochemistryDeath-ligand 1Metastatic gastric cancerPD-L1-positive samplesInter-assay concordanceCheckpoint inhibitorsDako 22C3ICI therapyCross-sectional studyCancer immunotherapyPatient selectionIntegration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis
Gwee Y, Chia D, So J, Ceelen W, Yong W, Tan P, Ong C, Sundar R. Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis. Journal Of Clinical Oncology 2022, 40: 2830. PMID: 35649219, PMCID: PMC9390822, DOI: 10.1200/jco.21.02745.Peer-Reviewed Original ResearchConceptsPeritoneal metastasisSystemic therapyClinical trialsGastric cancerTherapeutic strategiesEmergence of novel therapiesSynchronous peritoneal metastasesKnowledge of cancer biologyTraditional systemic therapiesCurrent standard-of-careSite of metastasisGastric cancer peritoneal metastasisAdvanced gastric cancerSurrounding tumor microenvironmentStandard-of-careInternational clinical guidelinesLocoregional therapeutic strategiesDiagnostic laparoscopyDismal prognosisTumor microenvironmentClinical entityNovel therapiesSurgical techniqueDisease stageMolecular profilingChoice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy.
Tay R, Yeong J, Lum J, Teo C, Tan B, Chan Y, Choo J, Jeyasekhran A, Miow Q, Loo L, Yong W, Sundar R. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Journal Of Clinical Oncology 2022, 40: 4026-4026. DOI: 10.1200/jco.2022.40.16_suppl.4026.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmune checkpoint inhibitor therapyPD-L1 CPSTumor proportion scorePD-L1Gastric cancerTissue microarrayImmune cellsPatients treated with ICI therapyPD-L1 expression statusPD-L1 immunohistochemistry assaysProgrammed death-ligand 1Resection of gastric cancerStandard-of-care treatmentGastric cancer immunotherapyPD-L1 scoringPD-L1 immunohistochemistryPD-L1 positivityDeath-ligand 1Metastatic gastric cancerPD-L1-positive samplesInter-assay concordanceNational University HospitalWhole slide analysisCut-offSingle-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric CancerSingle-Cell Atlas of Gastric Cancer Subtypes
Kumar V, Ramnarayanan K, Sundar R, Padmanabhan N, Srivastava S, Koiwa M, Yasuda T, Koh V, Huang K, Tay S, Ho S, Tan A, Ishimoto T, Kim G, Shabbir A, Chen Q, Zhang B, Xu S, Lam K, Lum H, Teh M, Yong W, So J, Tan P. Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric CancerSingle-Cell Atlas of Gastric Cancer Subtypes. Cancer Discovery 2022, 12: 670-691. PMID: 34642171, PMCID: PMC9394383, DOI: 10.1158/2159-8290.cd-21-0683.Peer-Reviewed Original ResearchConceptsPatient-derived organoidsPlasma cell proportionsGastric cancer subtypesLineage statePredictors of poor clinical prognosisCancer subtypesSingle-cell atlasCell proportionCancer-associated fibroblasts' subtypesCell populationsDiffuse-type tumorsPoor clinical prognosisIn vivo modelsComprehensive single-cell atlasPrimary tumorHistological subtypesRNA-sequencing cohortsTumor microenvironmentClinical stageClinical prognosisGastric malignancyTumor ecosystemGastric cancerCancer heterogeneityTumor
2021
Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Sundar R, Huang K, Kumar V, Ramnarayanan K, Demircioglu D, Her Z, Ong X, Bin Adam Isa Z, Xing M, Tan A, Tai D, Choo S, Zhai W, Lim J, Thakur M, Molinero L, Cha E, Fasso M, Niger M, Pietrantonio F, Lee J, Jeyasekharan A, Qamra A, Patnala R, Fabritius A, De Simone M, Yeong J, Ng C, Rha S, Narita Y, Muro K, Guo Y, Skanderup A, So J, Yong W, Chen Q, Göke J, Tan P. Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition. Gut 2021, 71: 1277-1288. PMID: 34433583, PMCID: PMC9185816, DOI: 10.1136/gutjnl-2021-324420.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionImmune microenvironmentHuman immune systemCheckpoint inhibitionActive human immune systemGastric cancerHuman T-cell infiltrationT cell cytolytic activityResistance to immune checkpoint inhibitionImmune systemProgression-free survivalImmunotherapy-treated patientsT cell infiltrationTumor immune microenvironmentT cell proportionsImmune-editingImmunotherapy resistanceFunctional in vivo studiesTumor kineticsHumanised miceAlternative promoter useTumor microenvironmentTherapeutic responseCytolytic activityImmune depletionMachine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial
Sundar R, Kumarakulasinghe N, Chan Y, Yoshida K, Yoshikawa T, Miyagi Y, Rino Y, Masuda M, Guan J, Sakamoto J, Tanaka S, Tan A, Hoppe M, Jeyasekharan A, Ng C, De Simone M, Grabsch H, Lee J, Oshima T, Tsuburaya A, Tan P. Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial. Gut 2021, 71: 676-685. PMID: 33980610, PMCID: PMC8921574, DOI: 10.1136/gutjnl-2021-324060.Peer-Reviewed Original ResearchConceptsDisease free survivalValidation cohortGastric cancerGene signatureSurvival benefitPac-SensitiveNo survival differenceSelection of patientsGC trialsFree survivalPaclitaxel chemotherapyCurative surgeryMetastatic patientsPredictive biomarkersTraining cohortSurvival differencesIndependent cohortNanoString panelGC patientsPaclitaxelPatientsNanoString profilingCohortGroup trialUFT