2019
A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors
Gaillard SL, Zahurak M, Sharma A, Durham J, Reiss K, Sartorius‐Mergenthaler S, Downs M, Anders N, Ahuja N, Rudek M, Azad N. A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors. Cancer 2019, 125: 2837-2845. PMID: 31012962, PMCID: PMC6663621, DOI: 10.1002/cncr.32138.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAnorexiaAntineoplastic Combined Chemotherapy ProtocolsAzacitidineDepsipeptidesDNA Modification MethylasesDrug Administration ScheduleFemaleHistone Deacetylase InhibitorsHumansLong Interspersed Nucleotide ElementsMaleMaximum Tolerated DoseMethyltransferasesMiddle AgedNauseaNeoplasmsConceptsHistone deacetylase inhibitor romidepsinDisease control rateAdvanced solid tumorsPhase 1 studyCC-486Solid tumorsDose-escalation portionPhase 2 doseDose-limiting toxicityPossible clinical benefitPhase 1 trialDose-escalation designElement-1 methylationLINE-1 methylationStable diseaseCommon toxicitiesDose expansionExpansion cohortPrimary outcomeClinical benefitControl rateDrug exposureBlood samplesDay 1Dose levels
2018
A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan
Lee V, Wang J, Zahurak M, Gootjes E, Verheul H, Parkinson R, Kerner Z, Sharma A, Rosner G, De Jesus-Acosta A, Laheru D, Le DT, Oganesian A, Lilly E, Brown T, Jones P, Baylin S, Ahuja N, Azad N. A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan. Clinical Cancer Research 2018, 24: 6160-6167. PMID: 30097434, DOI: 10.1158/1078-0432.ccr-18-0421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsAzacitidineColorectal NeoplasmsDNA MethylationEpigenesis, GeneticFemaleHumansIrinotecanLong Interspersed Nucleotide ElementsMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingRetreatmentTreatment OutcomeConceptsMetastatic colorectal cancerNeutropenic feverMetastatic colorectal cancer patientsDurable partial responseMost common toxicitiesDose-escalation studyColorectal cancer patientsInjection site reactionsOngoing phase IIPhase I trialInitial disease progressionCycles of treatmentCommon toxicitiesDrain infectionEvaluable patientsStable diseaseColonic obstructionPartial responseI trialMulticenter trialColorectal cancerGastrointestinal cancerSite reactionsCancer patientsDisease progression
2017
Long‐term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer
Shrestha B, Sun Y, Faisal F, Kim V, Soares K, Blair A, Herman JM, Narang A, Dholakia AS, Rosati L, Hacker‐Prietz A, Chen L, Laheru DA, De Jesus‐Acosta A, Le DT, Donehower R, Azad N, Diaz LA, Murphy A, Lee V, Fishman EK, Hruban RH, Liang T, Cameron JL, Makary M, Weiss MJ, Ahuja N, He J, Wolfgang CL, Huang C, Zheng L. Long‐term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer. Cancer Medicine 2017, 6: 1552-1562. PMID: 28639410, PMCID: PMC5504321, DOI: 10.1002/cam4.1104.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCombined Modality TherapyFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaleMiddle AgedNeoplasm StagingOdds RatioPancreatic NeoplasmsProportional Hazards ModelsSurvival RateTreatment OutcomeConceptsMedian overall survivalUpfront chemotherapyNeoadjuvant chemotherapyNeoadjuvant therapySurgical resectionOverall survivalUpfront chemoradiationBorderline resectable pancreatic adenocarcinomaLong-term survival benefitBorderline resectable pancreatic cancerCurative surgical resectionResectable pancreatic cancerUpfront neoadjuvant chemotherapyResectable pancreatic adenocarcinomaSubpopulation of patientsJohns Hopkins HospitalLong-term survivalCurative intentNeoadjuvant chemoradiationConsecutive patientsSurvival benefitPancreatic cancerPancreatic adenocarcinomaRetrospective analysisChemoradiationEpigenetic therapy and chemosensitization in solid malignancy
Ronnekleiv-Kelly SM, Sharma A, Ahuja N. Epigenetic therapy and chemosensitization in solid malignancy. Cancer Treatment Reviews 2017, 55: 200-208. PMID: 28431263, DOI: 10.1016/j.ctrv.2017.03.008.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicDrug Resistance, NeoplasmEpigenesis, GeneticGenetic TherapyHistone Deacetylase InhibitorsHumansMethyltransferasesNeoplasmsConceptsCombination therapyEpigenetic therapySpecific hematologic malignanciesCertain solid tumorsHistone deacetylase inhibitorsDurable responsesSystemic therapyPatient subsetsSolid malignanciesHematologic malignanciesOvarian cancerBreast cancerDNA methyltransferase inhibitorEpigenetic changesSolid tumorsDeacetylase inhibitorsStandard chemotherapeuticsTherapyClinical potentialCancer cellsTrialsNSCLCMalignancyMethyltransferase inhibitorHypermethylation patternsCombination 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 ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsAzacitidineBenzamidesCell Line, TumorCohort StudiesColorectal NeoplasmsDNA MethylationDrug Administration ScheduleEpigenesis, GeneticFemaleHCT116 CellsHumansMaleMiddle AgedPyridinesSurvival AnalysisTreatment OutcomeConceptsCombination 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
Epigenetic Therapeutics: A New Weapon in the War Against Cancer
Ahuja N, Sharma AR, Baylin SB. Epigenetic Therapeutics: A New Weapon in the War Against Cancer. Annual Review Of Medicine 2016, 67: 73-89. PMID: 26768237, PMCID: PMC4937439, DOI: 10.1146/annurev-med-111314-035900.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsChromatinClinical Trials as TopicCombined Modality TherapyDNA MethylationEpigenesis, GeneticHistone Deacetylase InhibitorsHumansImmunotherapyMethyltransferasesNeoplasmsRNA, UntranslatedConceptsEpigenetic therapyPrimary base sequenceNucleosome positioningEpigenetic regulationCellular regulationHeritable patternsEpigenetic mechanismsDNA methylationExplosion of discoveriesGene expressionCancer initiationBase sequenceEpigenomeRegulationFrequent mutationsGenetic abnormalitiesNormal maturationTumor cellsPotent toolChromatinCellsNeoplastic cellsGenesMethylationProtein
2015
Epigenetic therapy for solid tumors: from bench science to clinical trials
Juo YY, Gong XJ, Mishra A, Cui X, Baylin SB, Azad NS, Ahuja N. Epigenetic therapy for solid tumors: from bench science to clinical trials. Epigenomics 2015, 7: 215-235. PMID: 25942532, DOI: 10.2217/epi.14.73.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicDNA MethylationEpigenesis, GeneticHistone Deacetylase InhibitorsHumansNeoplasmsConceptsEpigenetic agentsCpG island promotersSolid tumorsGlobal DNA methylationOptimal patient selectionTumor suppressor geneNew therapeutic modalitiesChromatin changesCancer epigenomeHistone deacetylase inhibitorsDNA methylationDNA methyltransferaseEpigenetic therapyHormonal therapyDrug regimenSuppressor genePatient selectionFuture trialsHematologic malignanciesRecent trialsClinical trialsSignificant efficacyTherapeutic modalitiesPhenotype changesDeacetylase inhibitors
2014
The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma
Wu W, He J, Cameron JL, Makary M, Soares K, Ahuja N, Rezaee N, Herman J, Zheng L, Laheru D, Choti MA, Hruban RH, Pawlik TM, Wolfgang CL, Weiss MJ. The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma. Annals Of Surgical Oncology 2014, 21: 2873-2881. PMID: 24770680, PMCID: PMC4454347, DOI: 10.1245/s10434-014-3722-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantCombined Modality TherapyFemaleFollow-Up StudiesHumansMaleMiddle AgedNeoplasm StagingPancreatic NeoplasmsPancreaticoduodenectomyPostoperative ComplicationsPrognosisRadiotherapy, AdjuvantRetrospective StudiesSurvival RateConceptsAdjuvant therapyPostoperative complicationsMedian survivalMultivariate analysisClavien-Dindo complication gradeTherapy warrants further investigationMultimodality adjuvant therapyOverall complication rateMethodsA retrospective reviewGrade of complicationsLonger median survivalLength of stayWarrants further investigationAdjuvant chemotherapyMedian TTANeoadjuvant approachComplication gradeComplication rateSevere complicationsRetrospective reviewClinicopathological dataResultsA totalPancreaticoduodenectomyRadiation therapyComplications