Featured Publications
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 depletion
2022
Regulatory 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 survival
2019
DNA epigenetic signature predictive of benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma: results from the MRC OE02 trial
Sundar R, Ng A, Zouridis H, Padmanabhan N, Sheng T, Zhang S, Lee M, Ooi W, Qamra A, Inam I, Hewitt L, So J, Koh V, Nankivell M, Langley R, Allum W, Cunningham D, Rozen S, Yong W, Grabsch H, Tan P. DNA epigenetic signature predictive of benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma: results from the MRC OE02 trial. European Journal Of Cancer 2019, 123: 48-57. PMID: 31655359, DOI: 10.1016/j.ejca.2019.09.016.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCisplatinDNA MethylationEpigenesis, GeneticEsophageal NeoplasmsFemaleFluorouracilHumansMaleMiddle AgedNeoadjuvant TherapyNeoplasm GradingNeoplasm StagingPrognosisProportional Hazards ModelsRandomized Controlled Trials as TopicSurvival RateConceptsCS armNeoadjuvant chemotherapyOverall survivalOesophageal adenocarcinomaDNA methylation signaturesHistological subtypes of oesophageal cancerOesophageal cancerIndependent cohortPredictive of chemotherapy benefitSubtypes of oesophageal cancerIndependent cohort of patientsS armCox proportional hazards analysisResectable oesophageal cancerCohort of patientsPredictive of benefitMethylation signaturesDNA methylationPredictive of survivalProportional hazards analysisChemotherapy benefitHistological subtypesMetagene signatureRandomised patientsDNA methylation status