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
Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis
Chan J, Zhang B, Chew X, Salhi A, Kwok Z, Lim C, Desi N, Subramaniam N, Siemens A, Kinanti T, Ong S, Sanchez-Mejias A, Ly P, An O, Sundar R, Fan X, Wang S, Siew B, Lee K, Chong C, Lieske B, Cheong W, Goh Y, Fam W, Ooi M, Koh B, Iyer S, Ling W, Chen J, Yoong B, Chanwat R, Bonney G, Goh B, Zhai W, Fullwood M, Wang W, Tan K, Chng W, Dan Y, Pitt J, Roca X, Guccione E, Vardy L, Chen L, Gao X, Chow P, Yang H, Tay Y. Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis. Nature Cell Biology 2022, 24: 928-939. PMID: 35618746, PMCID: PMC9203280, DOI: 10.1038/s41556-022-00913-z.Peer-Reviewed Original ResearchConceptsUntranslated regionProtein-coding alterationsPost-transcriptional regulationAnti-cancer therapeuticsMammalian genesAlternative polyadenylationPan-cancer landscapeSplicing studiesAntisense oligonucleotide-mediated inhibitionUTR variantsDysregulation eventsSplicingOncogenic functionActivated oncogenesOncogene expressionMessenger RNAOncogeneTumor progressionPolyadenylationPoor prognosisHepatocellular carcinomaUpregulationColon adenocarcinomaGenesRNA
2020
Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model
Tan H, Kim G, Charles C, Li R, Jang C, Shabbir A, Chue K, Tai C, Sundar R, Goh B, Bonney G, Looi W, Cheow E, So J, Wang L, Yong W. Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model. European Journal Of Surgical Oncology 2020, 47: 1124-1131. PMID: 32800400, DOI: 10.1016/j.ejso.2020.06.031.Peer-Reviewed Original ResearchConceptsSolvent-based paclitaxelAdverse eventsGrade 2 hypersensitivity reactionSystemic exposure to paclitaxelAbsolute neutrophil countExposure to paclitaxelPhase I studyShort-term safetySignificant adverse eventsTissue drug concentrationsConcentrations of paclitaxelPotential adverse eventsYorkshire x Landrace pigsPeritoneal carcinomatosisPeritoneal biopsiesNeutrophil countPeritoneal surfaceToxicity profileBlood countIV infusionPeritoneal cavityPharmacokinetic analysisClinical trialsHigh dosesPharmacokinetic comparison
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-5478
2017
Combining DNA damaging therapeutics with immunotherapy: more haste, less speed
Brown J, Sundar R, Lopez J. Combining DNA damaging therapeutics with immunotherapy: more haste, less speed. British Journal Of Cancer 2017, 118: 312-324. PMID: 29123260, PMCID: PMC5808021, DOI: 10.1038/bjc.2017.376.Peer-Reviewed Educational MaterialsConceptsImmunogenic cell deathDNA-damaging therapeuticsPromote immunogenic cell deathPhase I-III trialsDurable response rateDNA-damaging agentsAntitumour immune responseRegimens to patientsProperties of malignant cellsChoice of combinationsCell deathAntitumour immunitySequence of agentsNeoantigen productionTumor microenvironmentMalignant cellsNeoantigen repertoireInflammatory milieuPreclinical workImmune cellsCombination trialsDamaging agentsImmunological memoryMinimal toxicityHypothesis-driven trialTargeting BRAF-Mutant Colorectal Cancer: Progress in Combination Strategies
Sundar R, Hong D, Kopetz S, Yap T. Targeting BRAF-Mutant Colorectal Cancer: Progress in Combination Strategies. Cancer Discovery 2017, 7: 558-560. PMID: 28576843, PMCID: PMC5458523, DOI: 10.1158/2159-8290.cd-17-0087.Commentaries, Editorials and Letters
2014
Immunotherapy in the treatment of non-small cell lung cancer
Sundar R, Soong R, Cho B, Brahmer J, Soo R. Immunotherapy in the treatment of non-small cell lung cancer. Lung Cancer 2014, 85: 101-109. PMID: 24880938, PMCID: PMC4332778, DOI: 10.1016/j.lungcan.2014.05.005.Peer-Reviewed Educational MaterialsConceptsImmune response to tumorsTreatment of non-small cell lung cancerNon-small cell lung cancerProlonged clinical responsesImmune checkpoint modulatorsImmune checkpoint pathwaysPD-L1 inhibitorsResponse to tumorsCell lung cancerCTLA-4PD-1PD-L1Tolerable toxicityTumor immunosurveillanceCheckpoint modulatorsCo-stimulatoryCo-inhibitoryClinical responseImmunotherapeutic agentsPredictive biomarkersImmune destructionLung cancerTreatment selectionImmune systemInhibitory molecules