Tobias Hartwich, PhD
Associate Research ScientistAbout
Research
Publications
2026
Remarkable preclinical activity of trastuzumab-deruxtecan (T-DXd) in FISH-negative, HER2 IHC 1+ and 2+ expressing primary endometrial cancer cell lines and xenografts
Palmieri L, Bellone S, Demirkiran C, Hartwich T, Sethi N, Ettorre V, Ottum S, Greenman M, Buza N, Hui P, Perrone E, Fanfani F, Fagotti A, Ratner E, Santin A. Remarkable preclinical activity of trastuzumab-deruxtecan (T-DXd) in FISH-negative, HER2 IHC 1+ and 2+ expressing primary endometrial cancer cell lines and xenografts. Gynecologic Oncology 2026, 206: 65-73. PMID: 41690203, DOI: 10.1016/j.ygyno.2026.02.004.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2T-DXdAntibody-drug conjugatesPreclinical activityEndometrial cancer patientsLow HER2 expressionFISH-negativeXenograft mouse modelTrastuzumab deruxtecanHER2 expressionCell linesHuman epidermal growth factor receptor 2 expressionCancer patientsMouse modelEpidermal growth factor receptor 2In vivoIn vitroAntibody-dependent cell cytotoxicityControl ADCEndometrial cancer cell linesHER2-overexpressing tumorsEffective treatment optionTumor growth suppressionHER2-lowStandard chemotherapyRemarkable preclinical activity of trastuzumab-deruxtecan (T-dxd) in FISH-negative, HER2 IHC 1+ and 2+ expressing primary endometrial cancer cell lines and xenografts
Palmieri L, Bellone S, Demirkiran C, Sethi N, Ottum S, Ettorre V, Greenman M, Hartwich T, Buza N, Hui P, Perrone E, Fanfani F, Fagotti A, Santin A. Remarkable preclinical activity of trastuzumab-deruxtecan (T-dxd) in FISH-negative, HER2 IHC 1+ and 2+ expressing primary endometrial cancer cell lines and xenografts. International Journal Of Gynecological Cancer 2026, 36: 103013. DOI: 10.1016/j.ijgc.2025.103013.Peer-Reviewed Original ResearchIntegrated mutational landscape analysis of endometrial stromal sarcoma
Hartwich T, Choi S, Hwang A, Bellone S, Palmieri L, Seo H, Kim T, Hong J, Krakstad C, Trovik J, Stefansson I, Haugland H, Greenman M, Ettorre V, Ottum S, Demirkiran C, Yang-Hartwich Y, Buza N, Hui P, Lopez S, Cormio G, Ramunno M, Zito A, Perrone E, Fagotti A, Fanfani F, Santoro A, Ravaggi A, Bignotti E, Odicino F, Ardighieri L, Ratner E, Angioli R, Perrone G, Luvero D, Conca B, Choi J, Schlessinger J, Santin A. Integrated mutational landscape analysis of endometrial stromal sarcoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2026, 123: e2531105123. PMID: 41591910, PMCID: PMC12867622, DOI: 10.1073/pnas.2531105123.Peer-Reviewed Original ResearchConceptsEndometrial stromal sarcomaHG-ESSStromal sarcomaLG-ESSFrequent lossMolecular basisHigh-gradeLow-gradePrediction of immunotherapy responseLoss of cell cycle regulationCell cycle regulationComplex DNA rearrangementsRare uterine malignancyCombination of MEKMutational landscape analysisDriver of malignancyTargeted treatment strategiesWhole genomeDNA rearrangementsFAK inhibitionTranscriptome sequencingWhole exomeGenetic landscapeChromosomal gainsRegulated genes
2025
Antibody Generation Using Cancer‐Derived Small Extracellular Vesicles (sEVs): A Platform for Targeted Cancer Therapy and Potential Personalized Applications
Firouzi M, Kang C, Ren X, Jung W, Abushukair H, Hartwich T, Ramesh R, Yoon J, Yang‐Hartwich Y, Oh T, Kim D. Antibody Generation Using Cancer‐Derived Small Extracellular Vesicles (sEVs): A Platform for Targeted Cancer Therapy and Potential Personalized Applications. Small 2025, 22: e06918. PMID: 41311345, DOI: 10.1002/smll.202506918.Peer-Reviewed Original ResearchTargeted cancer therapySmall extracellular vesiclesOVCAR-8Cancer therapyCancer-derived small extracellular vesiclesHuman ovarian carcinoma cell linesOvarian carcinoma cell linesCancer cell-specific targetingTumor-bearing miceTumor-targeting monoclonal antibodiesTumor-targeted therapyExtracellular vesiclesOVCAR-8 cellsCell-specific targetingCarcinoma cell linesEffective targeting ligandCancer-derivedSolid tumorsImmune activationNon-targeting controlPreclinical studiesTumor growthTumor accumulationPersonalized oncologyImmune responseFolate receptor alpha as a successful biomarker in the treatment of low-grade serous ovarian cancer patients using preclinical and clinical models
Ettorre V, Conca B, Demirkiran C, Bellone S, Sethi N, Hartwich T, Niu N, Buza N, Angioli R, Plotti F, Palmieri L, Santin A. Folate receptor alpha as a successful biomarker in the treatment of low-grade serous ovarian cancer patients using preclinical and clinical models. International Journal Of Gynecological Cancer 2025, 36: 102779. PMID: 41411700, DOI: 10.1016/j.ijgc.2025.102779.Peer-Reviewed Original ResearchLGSOC patientsLow-grade serous ovarian cancerSerous ovarian cancer patientsOvarian cancer patientsPatient-derived xenograft modelsSerous ovarian cancerMirvetuximab soravtansineStandard treatment modalityOvarian cancerFOLR1 expressionCancer patientsXenograft modelTreatment modalitiesRecurrent low-grade serous ovarian cancersResistant to standard treatment modalitiesClinical activitySerous ovarian cancer casesEpithelial ovarian cancer subtypesSevere combined immunodeficient miceProlonged partial responseOvarian cancer casesMEK inhibitor treatmentOvarian cancer subtypesMonths of treatmentResistance to chemotherapyImmunohistochemistry, next generation sequencing (NGS), and whole exome sequencing concordance in HER2 testing in uterine serous carcinoma: a retrospective analysis
Ettorre V, Bellone S, Buza N, Hui P, Hartwich T, Demirkiran C, Greenman M, Sethi N, Palmieri L, Santin A. Immunohistochemistry, next generation sequencing (NGS), and whole exome sequencing concordance in HER2 testing in uterine serous carcinoma: a retrospective analysis. Gynecologic Oncology 2025, 202: 131-136. PMID: 41092695, DOI: 10.1016/j.ygyno.2025.09.017.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaWhole-exome sequencingFluorescent-in-situ hybridizationNext generation sequencingHER2-positiveSerous carcinomaImmunohistochemistry stainingCorrelation of HER2HER2-Targeted TherapyHER2-targeted treatmentTissue blocksGeneration sequencingTreatment-eligible patientsComprehensive whole-exome sequencingEvaluation of patientsNext generation sequencing dataNext generation sequencing platformsFluorescence in situ hybridizationUSC patientsHER2 testingERBB2 amplificationHER2 expressionTherapeutic optionsRetrospective analysisHER2IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers
Zhang X, Xiao Q, Zeng L, Hashmi F, Sato K, Hartwich T, Mansolf M, Yang-Hartwich Y, Su X. IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers. Nature Chemical Biology 2025, 22: 379-391. PMID: 41023404, PMCID: PMC12825998, DOI: 10.1038/s41589-025-02031-x.Peer-Reviewed Original ResearchCAR-TChimeric antigen receptor (CAR)-T cell therapyCAR-T therapyCancer cells in vitroRelease of cytotoxic factorsCAR-T functionSolid tumor modelsAbsence of antigenLow antigen expressionCells in vitroMembrane-proximal signalingAntigen expressionAntigen sensitizationAntitumor effectCell therapyTumor modelIntractable cancerCytotoxic factorKilling activityBlood cancerCancerCancer targetLow antigenicityTherapyEfficacyPreclinical 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 assay