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
2020
Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma
Chong W, Lim C, Sinha A, Tan C, Chan G, Huang Y, Kumarakulasinghe N, Sundar R, Jeyasekharan A, Loh W, Tay J, Yadav K, Wang L, Wong A, Kong L, Soo R, Lau J, Soon Y, Goh R, Ho F, Chong S, Lee S, Loh K, Tai B, Lim Y, Goh B. Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma. Clinical Cancer Research 2020, 26: 5320-5328. PMID: 32816944, DOI: 10.1158/1078-0432.ccr-20-1727.Peer-Reviewed Original ResearchConceptsLocally advanced nasopharyngeal carcinomaAdvanced nasopharyngeal carcinomaNasopharyngeal carcinomaConcurrent chemoradiationGemcitabine chemotherapyArm CIncreased immune cell infiltrationComplete metabolic responsePosttreatment tumor biopsiesAnti-VEGF therapyArm A patientsRelapse-free survivalMetastatic nasopharyngeal carcinomaImmune cell infiltrationImmune cell traffickingVEGF axisTumor responseInduction cisplatinAntiangiogenic therapyTumor biopsiesTumor perfusionA patientsFDG-PETPericyte coverageStandard treatment
2019
Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy
Wang W, Xiang P, Chew W, Torta F, Bandla A, Lopez V, Seow W, Lam B, Chang J, Wong P, Chayaburakul K, Ong W, Wenk M, Sundar R, Herr D. Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy. Journal Of Biological Chemistry 2019, 295: 1143-1152. PMID: 31882542, PMCID: PMC6983853, DOI: 10.1074/jbc.ra119.011699.Peer-Reviewed Original ResearchConceptsChemotherapy-induced neuropathyRat model of cisplatin-induced neuropathyManagement of chemotherapy-induced neuropathyTreatment of chemotherapy-induced neuropathyS1P speciesEffects of platinum-based drugsCisplatin-induced neuropathyPlasma S1P levelsDorsal root gangliaS1P<sub>1-5</sub>Human cancer patientsActivating stress-response proteinsPlatinum-based drugsReduced allodyniaSphingosine 1-phosphateOxaliplatin treatmentPharmacodynamic analysisPeripheral neuropathyRat modelS1PCancer patientsLipid-based signaling moleculesS1P concentrationsS1P levelsCYM-5478DNA 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 statusRisk factors for chemotherapy‐induced peripheral neuropathy in patients receiving taxane‐ and platinum‐based chemotherapy
Molassiotis A, Cheng H, Leung K, Li Y, Wong K, Au J, Sundar R, Chan A, De Ng T, Suen L, Chan C, Yorke J, Lopez V. Risk factors for chemotherapy‐induced peripheral neuropathy in patients receiving taxane‐ and platinum‐based chemotherapy. Brain And Behavior 2019, 9: e01312. PMID: 31063261, PMCID: PMC6576180, DOI: 10.1002/brb3.1312.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyDevelopment of chemotherapy-induced peripheral neuropathyHistory of neuropathyRisk factorsPeripheral neuropathyPlatinum-based chemotherapySymptom burdenPotential risk factorsVegetable/fruit intakeWHO criteriaChemotherapy cyclesAlcohol intakeSmoking historyUnivariate analysisChemotherapyMultivariate regression modelMedical historyTreatment characteristicsNeurotoxic chemotherapyKey risk factorsNeuropathyCancer CenterSide effectsQuality of lifeTreatment decisions