2024
State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.
Balmaceda N, Petrillo A, Krishnan M, Zhao J, Kim S, Klute K, Sundar R. State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care. American Society Of Clinical Oncology Educational Book 2024, 44: e431060. PMID: 38771996, DOI: 10.1200/edbk_431060.Peer-Reviewed Original ResearchConceptsGastroesophageal cancerIntegration of immune checkpoint inhibitorsChimeric antigen receptor T cellsImmune checkpoint inhibitorsMetastatic gastroesophageal cancerPD-1 inhibitorsAdoptive cell therapyImmunotherapy-based approachesResectable gastroesophageal cancerAntibody-drug conjugatesCheckpoint inhibitorsPD-1Perioperative chemotherapyTargeted therapyT cellsTreatment paradigmFGFR2 inhibitorsCell therapyClinical challengeBispecific antibodiesImprove outcomesCancer treatmentReduced toxicityTherapyInhibitors
2023
Immune checkpoint inhibitor combinations—current and emerging strategies
Walsh R, Sundar R, Lim J. Immune checkpoint inhibitor combinations—current and emerging strategies. British Journal Of Cancer 2023, 128: 1415-1417. PMID: 36747017, PMCID: PMC10070427, DOI: 10.1038/s41416-023-02181-6.Peer-Reviewed Original Research
2022
Reply to: Letter to editor on the article “Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy”
Yeong J, Teo C, Tay R, Tan B, Chan Y, Smyth E, Sundar R. Reply to: Letter to editor on the article “Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy”. Gastric Cancer 2022, 25: 1133-1135. PMID: 36152122, DOI: 10.1007/s10120-022-01343-4.Peer-Reviewed Original ResearchResistance to systemic immune checkpoint inhibition in the peritoneal niche
Chia D, Gwee Y, Sundar R. Resistance to systemic immune checkpoint inhibition in the peritoneal niche. Journal For ImmunoTherapy Of Cancer 2022, 10: e004749. PMID: 35728873, PMCID: PMC9214396, DOI: 10.1136/jitc-2022-004749.Peer-Reviewed Original ResearchMeSH KeywordsAscitesHumansImmune Checkpoint InhibitorsImmunotherapyNeoplasmsPeritoneumTumor MicroenvironmentConceptsImmune checkpoint inhibitionResistance to immune checkpoint inhibitionPeritoneal metastasisCheckpoint inhibitionMetastatic nicheResponse to ICIImmune checkpoint inhibition therapySensitive to immune checkpoint inhibitionIntrinsic tumor factorsPresence of ascitesDeficient mismatch repairPeritoneal microenvironmentTumor factorsMalignant ascitesPrimary resistanceClinical entityTherapeutic optionsMicrosatellite instable tumorsPeritoneal cavityGastrointestinal cancerParacrine factorsAscitesConcurrent ascitesPatientsInstable tumorsChoice 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 ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCross-Sectional StudiesHumansImmunohistochemistryImmunotherapyStomach NeoplasmsConceptsCombined 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 selection
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 depletion
2020
Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers
Lee S, Shimasaki N, Lim J, Wong A, Yadav K, Yong W, Tan L, Koh L, Poon M, Tan S, Ow S, Bharwani L, Yap Y, Foo M, Coustan-Smith E, Sundar R, Tan L, Chong W, Kumarakulasinghe N, Lieow J, Koe P, Goh B, Campana D. Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers. Clinical Cancer Research 2020, 26: 4494-4502. PMID: 32522887, DOI: 10.1158/1078-0432.ccr-20-0768.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiopsyBreast NeoplasmsCoculture TechniquesCombined Modality TherapyDose-Response Relationship, DrugFemaleHumansImmunotherapyK562 CellsKiller Cells, NaturalMaleMiddle AgedReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsStomach NeoplasmsTransplantation, AutologousTrastuzumabConceptsAntibody-dependent cell cytotoxicityAutologous NK cellsNK cellsPhase I trialI trialNK cells expressed high levelsNatural killer (NK) cellsActivated autologous NK cellsHER2-positive solid tumorsPhase I dose escalationPeripheral blood NK cellsHER2-positive malignanciesNK cell infusionNK cell therapyBlood NK cellsNK cell expansionIncreased NK cellsPhase II trialPreliminary antitumor activityNK cell activityCells expressing high levelsHER2-positive cancersStable diseasePartial responseII trial
2019
Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer
Sundar R, Huang K, Qamra A, Kim K, Kim S, Kang W, Tan A, Lee J, Tan P. Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer. Annals Of Oncology 2019, 30: 424-430. PMID: 30624548, PMCID: PMC6442650, DOI: 10.1093/annonc/mdy550.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionMetastatic gastric cancerT cell cytolytic activityResistance to immune checkpoint inhibitionCheckpoint inhibitionGastric cancerCytolytic activityImmune evasionMedian progression-free survivalPhase II clinical trial of patientsCancer treated with immunotherapyClinical trials of patientsMechanisms of immune evasionResponse rateTreated with pembrolizumabPhase II clinical trialProgression-free survivalFresh tumor biopsiesPost-treatment biopsiesCohort of patientsTrial of patientsEarly gastric cancerArchival tissue samplesClinical responseTumor biopsies
2018
Resisting resistance to cancer immunotherapy
Lam W, Wang L, Roudi R, Yong W, Syn N, Sundar R. Resisting resistance to cancer immunotherapy. Thoracic Cancer 2018, 9: 507-508. PMID: 29512891, PMCID: PMC5928381, DOI: 10.1111/1759-7714.12614.Peer-Reviewed Original Research
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 Original ResearchConceptsImmunogenic 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 trial
2016
Emerging biomarkers for PD-1 pathway cancer therapy
Lim J, Sundar R, Chnard-Poirier M, Lopez J, Yap T. Emerging biomarkers for PD-1 pathway cancer therapy. Biomarkers In Medicine 2016, 11: 53-67. PMID: 27936870, DOI: 10.2217/bmm-2016-0228.Peer-Reviewed Original ResearchConceptsPD-L1Predictive biomarkers of responseImmune checkpoint inhibitorsImmune-related toxicitiesPD-L1 expressionPD-L1 inhibitorsBiomarkers of responseTreatment response biomarkersMultiple tumor typesIntermediate end pointsCheckpoint inhibitorsPD-1Predictive biomarkersImmuno-oncologyResponse assessmentTumor typesResponse biomarkersCancer therapyEnd pointsTherapy designBiomarkersFDA registrationTreatmentInhibitorsDifferential respondingTowards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics
Collins D, Sundar R, Lim J, Yap T. Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics. Trends In Pharmacological Sciences 2016, 38: 25-40. PMID: 27871777, DOI: 10.1016/j.tips.2016.10.012.Peer-Reviewed Original ResearchConceptsPrecision medicineNext-generation sequencingMechanisms of drug resistanceField of immunotherapyManagement of cancer patientsOptimize treatment efficacyAntitumor responseIntertumoral heterogeneityClonal evolutionTargeted agentsMinimal toxicityDrug resistanceCancer patientsTreatment efficacyBiomarker developmentBiomarker discoveryCancer researchCancerCompounds promisesImmunotherapyMedicine
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 Original ResearchConceptsImmune 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