Cem Demirkiran, MD
Postdoctoral AssociateAbout
Research
Publications
2025
Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK Clamp Avutometinib and FAK Inhibitor in a Low-Grade Serous Ovarian Cancer Animal Model with Acquired Resistance to Chemotherapy and Aromatase Inhibitor
Demirkiran C, Bellone S, Ettorre V, Mansolf M, Hartwich T, McNamara B, Greenman M, Yang-Hartwich Y, Ratner E, Santin N, Sethi N, Palmieri L, Coma S, Pachter J, Ottum S, Santin A. Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK Clamp Avutometinib and FAK Inhibitor in a Low-Grade Serous Ovarian Cancer Animal Model with Acquired Resistance to Chemotherapy and Aromatase Inhibitor. International Journal Of Molecular Sciences 2025, 26: 8924. PMID: 41009492, PMCID: PMC12469703, DOI: 10.3390/ijms26188924.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmFemaleFocal Adhesion Kinase 1FulvestrantHumansMiceMice, SCIDOvarian NeoplasmsProtein Kinase InhibitorsReceptors, EstrogenXenograft Model Antitumor AssaysConceptsPatient-derived tumor xenograftTriple combinationFocal adhesion kinasePreclinical efficacyAromatase inhibitorsClinical evaluationEstrogen receptor (ER)-positiveAcquired resistance to chemotherapyOvarian cancer animal modelEstrogen receptor degrader fulvestrantPatients wild-typeVS-4718Cancer animal modelTumor growth inhibitionLimited treatment optionsResistance to chemotherapyP-ERK levelsFocal adhesion kinase inhibitorMedian survivalRare tumorOvarian carcinomaRecurrence rateTumor xenograftsTreatment optionsFulvestrantEffective preclinical activity of datopotamab deruxtecan (Dato-DXd), an ADC targeting trophoblast cell-surface antigen 2 (TROP2), against primary cervical carcinoma cell lines and xenografts
Ettorre V, Demirkiran C, Bellone S, Hartwich T, Greenman M, McNamara B, Sethi N, Palmieri L, Santin A. Effective preclinical activity of datopotamab deruxtecan (Dato-DXd), an ADC targeting trophoblast cell-surface antigen 2 (TROP2), against primary cervical carcinoma cell lines and xenografts. Gynecologic Oncology 2025, 201: 195-202. PMID: 40907200, DOI: 10.1016/j.ygyno.2025.08.027.Peer-Reviewed Original ResearchTrophoblast cell surface antigen 2Primary cervical cancer cell linesAntibody-directed cellular cytotoxicityCervical cancer cell linesIn vivo anti-tumor activityAntibody-drug conjugatesCancer cell linesTumor cell deathTumor cellsNon-expressing cell linesCell linesTrophoblast cell surface antigen 2 expressionPreclinical pharmacologyClinical evaluationExpression of trophoblast cell surface antigen 2Cervical cancer mouse modelMedian overall survivalNegative tumor cellsCancer mouse modelCervical cancer patientsTumor growth suppressionCervical carcinoma cell linesCell deathCarcinoma cell linesMarkers of apoptosisPreclinical Activity of Datopotamab Deruxtecan (Dato-DXd), an Antibody–Drug Conjugate Targeting TROP2, in Poorly Differentiated Endometrial Carcinomas
Santin N, Sethi N, Bellone S, Demirkiran C, Ettorre V, Greenman M, McNamara B, Buza N, Hartwich T, Palmieri L, Lorusso D, Santin A. Preclinical Activity of Datopotamab Deruxtecan (Dato-DXd), an Antibody–Drug Conjugate Targeting TROP2, in Poorly Differentiated Endometrial Carcinomas. Cancer Research Communications 2025, 5: 1611-1620. PMID: 40862536, PMCID: PMC12423748, DOI: 10.1158/2767-9764.crc-25-0251.Peer-Reviewed Original ResearchConceptsEndometrial cancer cell linesTrophoblast antigen 2Antibody-dependent cell cytotoxicityAntibody-drug conjugatesEndometrial cancer xenograftsCancer cell linesEndometrial cancerPreclinical activityBystander killingCancer xenograftsCell linesPreclinical evidenceIn vivo activityCell cytotoxicityTargeted treatmentPrimary tumor cell linesBiomarker-targeted therapiesNovel antibody-drug conjugatesControl ADCRecurrent endometrial cancerChromium release assayFlow cytometry-based assayTumor growth inhibitionIn vivoCytometry-based assayDatopotamab deruxtecan, a novel TROP2-tareting antibody-drug conjugate with a topoisomerase I inhibitor payload, shows preclinical activity against primary and metastatic uterine and ovarian TROP2 over-expressing carcinosarcoma
Greenman M, Bellone S, Demirkiran C, Hartwich T, Ettorre V, McNamara B, Sethi N, Santin N, Palmieri L, Yang-Hartwich Y, Ratner E, Santin A. Datopotamab deruxtecan, a novel TROP2-tareting antibody-drug conjugate with a topoisomerase I inhibitor payload, shows preclinical activity against primary and metastatic uterine and ovarian TROP2 over-expressing carcinosarcoma. Gynecologic Oncology 2025, 199: 64-71. PMID: 40582040, DOI: 10.1016/j.ygyno.2025.06.017.Peer-Reviewed Original ResearchConceptsCS cell linesPreclinical activityTROP2 expressionPresence of peripheral blood lymphocytesTopoisomerase I inhibitor payloadCell linesRare gynecologic tumorsChromium release assayResistance to chemotherapyTumor growth suppressionPeripheral blood lymphocytesIn vivoAntibody-drug conjugatesOvarian carcinosarcomaRecurrence rateGynecological tumorsNo significant differencePreclinical resultsHealthy donorsBlood lymphocytesPoor prognosisMouse xenograftsChromium releaseClinical trialsCell cytotoxicityPreclinical activity of sacituzumab govitecan in TROP2-positive low-grade serous ovarian cancer patient-derived xenograft models
Ettorre V, Demirkiran C, Bellone S, Niu N, Buza N, Sethi N, Hartwich T, Palmieri L, Santin A. Preclinical activity of sacituzumab govitecan in TROP2-positive low-grade serous ovarian cancer patient-derived xenograft models. International Journal Of Gynecological Cancer 2025, 35: 101988. PMID: 40680453, DOI: 10.1016/j.ijgc.2025.101988.Peer-Reviewed Original ResearchConceptsLow-grade serous ovarian cancerTrophoblast cell surface antigen 2Serous ovarian cancerTrophoblast cell surface antigen 2 expressionSacituzumab govitecanOvarian cancerPatient-derived xenograftsPreclinical activityResistance to chemotherapyPDX modelsAromatase inhibitorsDisease resistant to chemotherapySerous ovarian cancer casesEpithelial ovarian cancer subtypesEffective new treatment optionPatient-derived xenograft modelsSevere combined immunodeficient miceModerate to strong expressionOvarian cancer casesIndolent disease courseOvarian cancer subtypesStandard treatment modalityNew treatment optionsCohort of patientsIn vivoA phase 2 trial of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability (NCT02899793): Updated survival and response analyses
Ettorre V, Bellone S, Greenman M, McNamara B, Palmieri L, Sethi N, Demirkiran C, Papatla K, Kailasam A, Siegel E, Ratner E, Santin A. A phase 2 trial of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability (NCT02899793): Updated survival and response analyses. Gynecologic Oncology 2025, 197: 110-115. PMID: 40334308, DOI: 10.1016/j.ygyno.2025.04.591.Peer-Reviewed Original ResearchProgression free survivalWhole-exome sequencingImmune checkpoint inhibitorsOverall survivalEndometrial cancerMicrosatellite instability-highCheckpoint inhibitorsFree survivalFollow-upResponse to immune checkpoint inhibitorsPatients treated with pembrolizumabProspective phase II studyExome sequencingResponse rateRecurrent platinum-resistantPhase II studyPhase 2 trialOverall survival dataEndometrial cancer patientsMLH-1MSI-H patientsFoundationOne platformImproved OSUpdate survivalPrognostic significancePreclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma.
Greenman M, Demirkiran C, Bellone S, Hartwich T, McNamara B, Ettorre V, Santin N, Sethi N, Yang-Hartwich Y, Papatla K, Ratner E, Santin A. Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma. Cancer Research Communications 2025, 5: 774-782. PMID: 40299780, PMCID: PMC12062949, DOI: 10.1158/2767-9764.crc-25-0057.Peer-Reviewed Original ResearchConceptsTrophoblast cell surface antigen 2Uterine serous carcinomaAntibody-dependent cell-mediated cytotoxicityAntibody-drug conjugatesCell-mediated cytotoxicitySerous carcinomaPreclinical activityCell linesTargets trophoblast cell-surface antigen-2Presence of peripheral blood lymphocytesTreatment of uterine serous carcinomaInduce antibody-dependent cell-mediated cytotoxicityPrimary USC cell linesRecurrent uterine serous carcinomaUSC xenograftsUterine serous carcinoma cell linesAntigen 2In vivoPrimary tumor cell linesTROP2 overexpressionBiomarker-targeted therapiesControl ADCChromium release assayHigher recurrence rateTumor growth suppressionActivity Restrictions After Midurethral Sling: A Randomized Controlled Trial.
Alvarez P, Demirkiran C, Rickey L, Lundsberg L, Harmanli O. Activity Restrictions After Midurethral Sling: A Randomized Controlled Trial. Urogynecology 2025 PMID: 40105744, DOI: 10.1097/spv.0000000000001679.Peer-Reviewed Original ResearchStress urinary incontinenceMUS surgeryPostoperative activity restrictionsPatient satisfactionUrinary incontinenceMidurethral sling (MUSActivity restrictionRandomized clinical trialsSatisfaction scoresActivity 3 weeksRandomized Controlled TrialsStatically significant differenceMidurethral slingIncontinence symptomsSurgical successPostoperative visitSurgical outcomesBaseline characteristicsHigh satisfactionHigher satisfaction scoresHigh-impact activitiesClinical trialsPrimary outcomeSurgeryPatient satisfaction scale
2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, PMCID: PMC12626252, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyUterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315)
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Schlessinger J, Santin A. Uterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315). Gynecologic Oncology 2023, 176: s193. DOI: 10.1016/j.ygyno.2023.06.218.Peer-Reviewed Original Research