2023
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltration
2022
A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence
Heumann T, Baretti M, Sugar E, Durham J, Linden S, Lopez-Vidal T, Leatherman J, Cope L, Sharma A, Weekes C, O’Dwyer P, Reiss K, Monga D, Ahuja N, Azad N. A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence. Clinical Epigenetics 2022, 14: 166. PMID: 36463226, PMCID: PMC9719150, DOI: 10.1186/s13148-022-01367-8.Peer-Reviewed Original ResearchConceptsResectable pancreatic ductal adenocarcinomaCC-486OBS patientsMetastatic settingAdjuvant therapyTreatment-related grade 3Randomized phase II studyMedian age 66Next-line therapyResultsForty-nine patientsMedian treatment durationPhase II studyEvidence of diseaseHigh-risk featuresPhase II trialProgression-free survivalStandard adjuvant therapyPancreatic ductal adenocarcinomaCancer recursEvaluable patientsMedian OSMedian PFSOral azacitidineR1 resectionSubsequent chemotherapy
2017
Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study
Azad NS, el-Khoueiry A, Yin J, Oberg AL, Flynn P, Adkins D, Sharma A, Weisenberger DJ, Brown T, Medvari P, Jones PA, Easwaran H, Kamel I, Bahary N, Kim G, Picus J, Pitot HC, Erlichman C, Donehower R, Shen H, Laird PW, Piekarz R, Baylin S, Ahuja N. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat; a phase 2 consortium/stand Up 2 cancer study. Oncotarget 2017, 5: 35326-35338. PMID: 28186961, PMCID: PMC5471058, DOI: 10.18632/oncotarget.15108.Peer-Reviewed Original ResearchConceptsCombination epigenetic therapyMetastatic colorectal cancerRECIST responseCRC patientsMedian progression-free survivalCycles of therapySignificant clinical activityMetastatic CRC patientsProgression-free survivalSubset of patientsM2 days 1Serial tumor biopsiesMulti-institutional studyHistone deacetylase inhibitor entinostatEpigenetic therapyColorectal cell linesSubcutaneous azacitidinePrimary endpointPrior therapyLiver involvementOverall survivalTolerable therapySerial biopsiesColorectal cancerClinical activity
2016
Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma
Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, Yang S, Duncan M, Ahuja N, Taube JM, Anders RA, Kelly RJ. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut 2016, 66: 794. PMID: 26801886, PMCID: PMC4958028, DOI: 10.1136/gutjnl-2015-310839.Peer-Reviewed Original ResearchConceptsPD-L1 expressionProgression-free survivalEpstein-Barr virusT-cell densityImmune stromaOverall survivalPD-L1T cellsAdaptive immune resistance mechanismHigh PD-L1 expressionMembranous PD-L1 expressionStromal PD-L1 expressionCD8 T cell infiltrationWorse progression-free survivalImmune resistance mechanismsImmune checkpoint inhibitorsPD-L1 positivityPD-L1 statusGastro-oesophageal junctionImmune-based therapiesT cell infiltrationPercentage of tumorsTumor-stromal interfaceCD8 densityCD8 infiltration
2011
OT3-01-06: A Phase 2 Study Investigating the Safety, Efficacy and Surrogate Biomarkers of Response of 5-Azacitidine (5-AZA) and Entinostat (MS-275) in Patients with Advanced Breast Cancer.
Connolly R, Jankowitz R, Andreopoulou E, Allred J, Jeter S, Zorzi J, Adam B, Espinoza-Delgado I, Baylin S, Zahnow C, Ahuja N, Davidson N, Stearns V. OT3-01-06: A Phase 2 Study Investigating the Safety, Efficacy and Surrogate Biomarkers of Response of 5-Azacitidine (5-AZA) and Entinostat (MS-275) in Patients with Advanced Breast Cancer. Cancer Research 2011, 71: ot3-01-06-ot3-01-06. DOI: 10.1158/0008-5472.sabcs11-ot3-01-06.Peer-Reviewed Original ResearchObjective response rateHistone deacetylase inhibitorsHormone-resistant diseaseAdvanced breast cancerBreast cancerDNA methyltransferase inhibitorHormonal therapyAdvanced human epidermal growth factor receptor 2Response rateMulticenter phase II studyHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Adequate organ functionClinical benefit rateRECIST 1.1 criteriaPhase II studyWeeks of therapyPhase 2 studyProgression-free survivalGrowth factor receptor 2Objective disease responseNegative breast cancerFactor receptor 2Important therapeutic targetCandidate gene methylation