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
2017
Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells
Siebenkäs C, Chiappinelli KB, Guzzetta AA, Sharma A, Jeschke J, Vatapalli R, Baylin SB, Ahuja N. Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells. PLOS ONE 2017, 12: e0179501. PMID: 28622390, PMCID: PMC5473589, DOI: 10.1371/journal.pone.0179501.Peer-Reviewed Original ResearchConceptsSubset of patientsOvarian cancer cell linesAntigen processingCancer cell linesImmune therapyCancer testisSolid tumorsCell linesCancer cellsCancer-testis antigensHost immune systemOvarian cancer cellsTreatment time pointsEpigenetic therapyRelevant low dosesPresentation machineryImmune cellsOvarian cancerAntigen presentationMurine modelTestis antigensInnovative therapiesImmune systemLow dosesTherapyEpigenetic 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 ResearchConceptsCombination therapyEpigenetic therapySpecific hematologic malignanciesCertain solid tumorsHistone deacetylase inhibitorsDurable responsesSystemic therapyPatient subsetsSolid malignanciesHematologic malignanciesOvarian cancerBreast cancerDNA methyltransferase inhibitorEpigenetic changesSolid tumorsDeacetylase inhibitorsStandard chemotherapeuticsTherapyClinical potentialCancer cellsTrialsNSCLCMalignancyMethyltransferase inhibitorHypermethylation patterns
2015
A phase I trial of oral 5-azacitidine in combination with romidepsin in advanced solid tumors with an expansion cohort in virally mediated cancers and liposarcoma.
Reiss K, Rudek M, Sartorius-Mergenthaler S, Downs M, Cosgrove D, Gaillard S, Baylin S, Ahuja N, Azad N. A phase I trial of oral 5-azacitidine in combination with romidepsin in advanced solid tumors with an expansion cohort in virally mediated cancers and liposarcoma. Journal Of Clinical Oncology 2015, 33: tps2619-tps2619. DOI: 10.1200/jco.2015.33.15_suppl.tps2619.Peer-Reviewed Original ResearchEpigenetic 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 ResearchConceptsEpigenetic 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
High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program
Moningi S, Armour EP, Terezakis SA, Efron JE, Gearhart SL, Bivalacqua TJ, Kumar R, Le Y, Ng S, Wolfgang CL, Zellars RC, Ellsworth SG, Ahuja N, Herman JM. High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program. Journal Of Contemporary Brachytherapy 2014, 6: 99-105. PMID: 24790628, PMCID: PMC4003434, DOI: 10.5114/jcb.2014.42027.Peer-Reviewed Original ResearchRate intraoperative radiation therapyIntraoperative radiation therapyRadiation therapyLocal controlGroup of patientsEffective local controlPelvic solid tumorsHDR-IORTRecurrent tumorsTrue efficacySolid tumorsMultidisciplinary approachPatientsTherapyTumorsIORT programProper administrationIORTSpecialized institutionsMalignancyOncologistsAnesthesiologistsPhysics staffNursesSurgeonsImmune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers
Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 2014, 5: 587-598. PMID: 24583822, PMCID: PMC3996658, DOI: 10.18632/oncotarget.1782.Peer-Reviewed Original ResearchConceptsDNA methyltransferase inhibitorImmune gene setsImmune-stimulatory roleCytokines/chemokinesCancer-testis antigensGene expression subsetsMethyltransferase inhibitorEpigenetic therapyHuman epithelial cancersMechanism of actionCancer cell linesPrimary tumorGene Set Enrichment AnalysisImmunomodulatory pathwaysImmune regulationPotential therapyTestis antigensPatient biopsiesSolid tumorsEpithelial cancersMultiple cancersLow dosesTumor expression dataAntigen processingTherapyHarnessing the potential of epigenetic therapy to target solid tumors
Ahuja N, Easwaran H, Baylin SB. Harnessing the potential of epigenetic therapy to target solid tumors. Journal Of Clinical Investigation 2014, 124: 56-63. PMID: 24382390, PMCID: PMC3871229, DOI: 10.1172/jci69736.Peer-Reviewed Original Research