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 ResearchConceptsMetastatic 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 progressionA novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent
Thakar M, Hu Y, Morreale M, Lerner L, Lin W, Sen R, Cai Y, Karunasena E, Thakar M, Saggi S, Keer H, Ahuja N. A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent. PLOS ONE 2018, 13: e0199130. PMID: 29927979, PMCID: PMC6013229, DOI: 10.1371/journal.pone.0199130.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaDNA methyltransferase 1Chemotherapeutic agent irinotecanEpigenetic modulating agentsPDAC cell linesCell viabilityMechanism of actionSystemic chemotherapyCancer mortalityChemotherapy responseDuctal adenocarcinomaChemotherapy agentsEpigenetic sensitizationModulating agentsGuadecitabineAdditional studiesPancreatic cellsSerial concentrationsRest periodCell linesNanomolar concentrationsImproved responseEpigenetic modulatorsSensitizationMethyltransferase 1
2017
Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells
Sharma A, Vatapalli R, Abdelfatah E, McMahon K, Kerner Z, Guzzetta A, Singh J, Zahnow C, Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLOS ONE 2017, 12: e0176139. PMID: 28445481, PMCID: PMC5405959, DOI: 10.1371/journal.pone.0176139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsATP-Binding Cassette TransportersAzacitidineCaco-2 CellsCamptothecinCell AdhesionCell Line, TumorCell ProliferationColorectal NeoplasmsDNA MethylationDNA RepairGene ExpressionGene Expression ProfilingHCT116 CellsHumansIrinotecanLong Interspersed Nucleotide ElementsMiceMice, Inbred NODMice, SCIDConceptsCRC cell linesColorectal cancerMultiple CRC cell linesPhase 1/2 clinical trialCell linesMetastatic colorectal cancerMajority of patientsNOD-SCID miceColorectal cancer cellsSoft agar assayInitial therapyMetastatic settingCytotoxic chemotherapyCRC treatmentClinical efficacyCancer deathTumor regressionClinical trialsDNA demethylating agentVivo xenograftsChemotherapeutic agentsCancer cellsHCT116 cell linesAgar assayChemotherapy