2024
A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS‐102 in irinotecan‐refractory metastatic colorectal cancer patients
Lee V, Parkinson R, Zahurak M, Cope L, Cercek A, Verheul H, Gootjes E, Lenz H, Iqbal S, Jones P, Baylin S, Rami V, Ahuja N, Khoueiry A, Azad N. A phase II study of guadecitabine combined with irinotecan vs regorafenib or TAS‐102 in irinotecan‐refractory metastatic colorectal cancer patients. International Journal Of Cancer 2024, 154: 1794-1801. PMID: 38312102, DOI: 10.1002/ijc.34845.Peer-Reviewed Original ResearchRefractory to irinotecanArm ATAS-102DNA methyltransferase inhibitorArm BRates of progression free survivalB. Median overall survivalEvidence of target modulationMetastatic colorectal cancer patientsResistant to systemic therapyTreatment related adverse eventsProgression free survivalPhase II studyPhase II trialKaplan-Meier ratesRelated adverse eventsColorectal cancer patientsFree survivalOverall survivalSystemic therapyAdverse eventsIrinotecanRegorafenibCancer patientsGuadecitabine
2020
Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer
Kim VM, Pan X, Soares KC, Azad NS, Ahuja N, Gamper CJ, Blair AB, Muth S, Ding D, Ladle BH, Zheng L. Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer. JCI Insight 2020, 5: e136368. PMID: 32376802, PMCID: PMC7253020, DOI: 10.1172/jci.insight.136368.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerColorectal cancerDNA methyltransferase inhibitorAntitumor efficacyAntigen-specific antitumor immune responsesAntitumor T-cell responsesCancer testis antigen expressionAntitumor immune responseT cell responsesAntitumor immunityCancer vaccinesSurvival outcomesCombination therapyAntigen expressionImmune responseMurine modelCTA expressionCell responsesNeoantigensImproved efficacyTumor cellsVaccineEfficacyGVAXMethyltransferase inhibitor
2018
Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma
De Carvalho Fischer C, Hu Y, Morreale M, Lin WY, Wali A, Thakar M, Karunasena E, Sen R, Cai Y, Murphy L, Zahnow CA, Keer H, Thakar M, Ahuja N. Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma. Oncotarget 2018, 9: 19379-19395. PMID: 29721210, PMCID: PMC5922404, DOI: 10.18632/oncotarget.25056.Peer-Reviewed Original ResearchDNA methyltransferase inhibitorEpigenetic modulatorsLMS cell linesCell linesMES-SAApoptotic pathwayCell cycleMethyltransferase inhibitorCell survivalDifferentiation patternsEpigenetic agentsNovel chemotherapeutic regimensPotential therapeutic applicationsLeiomyosarcoma cell lineRare mesenchymal neoplasmSpectrum of sensitivityChemotherapeutic regimensPoor prognosisMesenchymal neoplasmsSensitive linesTumor growthGuadecitabineTherapeutic applicationsAdditional studiesModulator
2017
Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study
Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff AC, Fetting JH, Brufsky A, Piekarz R, Ahuja N, Laird PW, Shen H, Weisenberger DJ, Cope L, Herman JG, Somlo G, Garcia AA, Jones PA, Baylin SB, Davidson NE, Zahnow CA, Stearns V. Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study. Clinical Cancer Research 2017, 23: 2691-2701. PMID: 27979916, PMCID: PMC5457329, DOI: 10.1158/1078-0432.ccr-16-1729.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerObjective response rateCombination epigenetic therapyEstrogen receptorEndocrine therapyPrimary endpointPartial responseMulticenter phase II studyEpigenetic therapyAdditional partial responsesHormone-resistant diseasePhase II studyTime of progressionBreast cancer modelClin Cancer ResHistone deacetylase inhibitorsImportant therapeutic targetPosttreatment biopsiesTNBC cohortII studyBreast cancerDNA methyltransferase inhibitorTherapeutic targetResponse rateCancer modelEpigenetic 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
2016
Combining Epigenetic and Immunotherapy to Combat Cancer
Chiappinelli KB, Zahnow CA, Ahuja N, Baylin SB. Combining Epigenetic and Immunotherapy to Combat Cancer. Cancer Research 2016, 76: 1683-1689. PMID: 26988985, PMCID: PMC4873370, DOI: 10.1158/0008-5472.can-15-2125.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitor efficacyCheckpoint inhibitor efficacyImmune checkpoint blockadeCurrent clinical trialsT-cell attractionException of melanomaAdvanced human cancersCancer management strategiesEpithelial cancer cellsCheckpoint blockadeMost patientsCombination therapyCancer testisClinical trialsDNA methyltransferase inhibitorMouse modelInhibitor efficacyImmune signalingCancer cellsHuman cancersMethyltransferase inhibitorEpigenetic drugsDemethylating agentExciting recent advancesEndogenous retroviruses
2014
Immune 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 processingTherapy
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