2024
Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma
McNamara B, Greenman M, Bellone S, Santin L, Demirkiran C, Mutlu L, Hartwich T, Yang-Hartwich Y, Ratner E, Schwartz P, Santin A. Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma. Gynecologic Oncology 2024, 189: 16-23. PMID: 38981151, DOI: 10.1016/j.ygyno.2024.07.002.Peer-Reviewed Original ResearchTargets trophoblast cell-surface antigen-2Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityPreclinical activityAntibody drug conjugatesOvarian cancerCell linesTumor cellsTrophoblast cell surface antigen 2Cell line-derived xenograft modelFlow cytometryCompared to tumor cellsEpithelial ovarian cancer cell linesOvarian cancer cell linesTumor cells in vitroOvarian cancer patientsPeripheral-blood lymphocytesEOC cell linesTumor growth suppressionAnnexin V-positiveGynecologic cancer mortalityIn vivo antitumor activityCells in vitroPrimary cell linesUnmet medical need
2022
Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor
Tymon-Rosario JR, Manara P, Manavella DD, Bellone S, Hartwich TMP, Harold J, Yang-Hartwich Y, Zipponi M, Choi J, Jeong K, Mutlu L, Yang K, Altwerger G, Menderes G, Ratner E, Huang GS, Clark M, Andikyan V, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a poly (adenosine diphosphate [ADP]- ribose) polymerase (PARP) inhibitor. Gynecologic Oncology 2022, 166: 117-125. PMID: 35599167, DOI: 10.1016/j.ygyno.2022.05.005.Peer-Reviewed Original ResearchConceptsUterine carcinosarcomaCS cell linesSignature 3Cell linesPolymerase inhibitorsOverall animal survivalFresh tumor samplesPoly (ADP-ribose) polymerase (PARP) inhibitorsXenograft tumor growthG2/M phaseAggressive malignancyCS patientsPrimary tumorCell cycle arrestPrimary cell linesPoor survivalClinical studiesPreclinical sensitivityCarcinosarcomaTumor growthAnimal survivalOlaparib activityTumor samplesOlaparibAntitumor activity
2019
PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib
Bianchi A, Lopez S, Altwerger G, Bellone S, Bonazzoli E, Zammataro L, Manzano A, Manara P, Perrone E, Zeybek B, Han C, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Newberg JY, Pavlick DC, Elvin J, Frampton GM, Schwartz PE, Santin AD. PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib. Gynecologic Oncology 2019, 155: 144-150. PMID: 31434613, PMCID: PMC6788971, DOI: 10.1016/j.ygyno.2019.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsApoptosisCell Growth ProcessesCell Line, TumorDose-Response Relationship, DrugDrug Resistance, NeoplasmFemaleG2 Phase Cell Cycle CheckpointsHumansM Phase Cell Cycle CheckpointsMice, SCIDMiddle AgedPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsPoly (ADP-ribose) polymerase (PARP) inhibitorsCervical cancerCC cell linesCell linesPARP-1 activityOverall animal survivalMajor health problemCC cell growthXenograft tumor growthWestern blot assaysG2/M phaseVivo antitumor activityCC xenograftsCC patientsPreclinical activityPAR expressionCell cycle arrestOvarian cancerPrimary cell linesOlaparib treatmentUseful biomarkerHealth problemsTumor growthAnimal survivalOlaparib activity
2018
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Li C, Bonazzoli E, Bellone S, Choi J, Dong W, Menderes G, Altwerger G, Han C, Manzano A, Bianchi A, Pettinella F, Manara P, Lopez S, Yadav G, Riccio F, Zammataro L, Zeybek B, Yang-Hartwich Y, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Zizioli V, Odicino F, Pecorelli S, Ardighieri L, Silasi DA, Litkouhi B, Ratner E, Azodi M, Huang GS, Schwartz PE, Lifton RP, Schlessinger J, Santin AD. Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 619-624. PMID: 30584090, PMCID: PMC6329978, DOI: 10.1073/pnas.1814027116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAzepinesBRCA1 ProteinBRCA2 ProteinCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMiceMutationNeoplasm MetastasisNeoplasm Recurrence, LocalOvarian NeoplasmsProteinsProto-Oncogene Proteins c-mycTriazolesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOvarian cancerWhole-exome sequencingC-myc amplificationRecurrent tumorsPrimary tumorBET inhibitorsChemotherapy-resistant diseaseRecurrent ovarian cancerLethal gynecologic malignancyBilateral ovarian cancerChemotherapy-resistant tumorsPrimary metastatic tumorsMutational landscapeSomatic mutationsFresh-frozen tumorsGynecologic malignanciesMetastatic tumorsPrimary cell linesC-MYC gainPIK3CA amplificationTranscoelomic metastasisTherapeutic targetPatientsMetastatic abilityTumors
2014
Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo
Schwab CL, English DP, Roque DM, Bellone S, Lopez S, Cocco E, Nicoletti R, Rutherford TJ, Schwartz PE, Santin AD. Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecologic Oncology 2014, 135: 142-148. PMID: 25124161, DOI: 10.1016/j.ygyno.2014.08.006.Peer-Reviewed Original ResearchConceptsHER2/neu amplificationUterine serous carcinomaHER2/neuUSC cell linesNeu amplificationNon-amplified cell linesSerous carcinomaCell linesTyrosine kinase inhibitor neratinibEffects of neratinibPrimary USC cell linesEndometrial cancer patientsPotential treatment optionEfficacy of neratinibG0/G1 phaseCell cycle distributionActivation of S6Overall survivalEndometrial cancerAggressive variantTreatment optionsCancer patientsClinical trialsPrimary cell linesHER2 inhibitors
2011
Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma
Bignotti E, Ravaggi A, Romani C, Falchetti M, Lonardi S, Facchetti F, Pecorelli S, Varughese J, Cocco E, Bellone S, Schwartz PE, Rutherford TJ, Santin AD. Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma. International Journal Of Gynecological Cancer 2011, 21: 1613-1621. PMID: 21892093, PMCID: PMC3233648, DOI: 10.1097/igc.0b013e318228f6da.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorComplement System ProteinsEndometrial NeoplasmsFemaleFlow CytometryHumansImmunization, PassiveImmunoglobulin GImmunohistochemistryRNA, MessengerConceptsEndometrial endometrioid carcinomaNormal endometrial controlsTrop-2 expressionEEC cell linesAntibody-dependent cellular cytotoxicityReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionEndometrioid carcinomaPolymerase chain reactionCellular cytotoxicityTrop-2Anti-Trop-2 antibodyCell linesTherapeutic agentsCr-release assaysTrop-2 overexpressionGrade 3 tumorsStandard treatment modalityChain reactionNovel therapeutic agentsCell surface markersEndometrial controlTreatment modalitiesPrimary cell linesEEC samples
2003
Selection of HER-2/neu-positive tumor cells in early stage cervical cancer: implications for Herceptin-mediated therapy
Bellone S, Palmieri M, Gokden M, Joshua J, Roman JJ, Pecorelli S, Cannon MJ, Santin AD. Selection of HER-2/neu-positive tumor cells in early stage cervical cancer: implications for Herceptin-mediated therapy. Gynecologic Oncology 2003, 91: 231-240. PMID: 14529687, DOI: 10.1016/s0090-8258(03)00460-8.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityEarly-stage cervical cancerStage cervical cancerCervical cancer cell linesCancer cell linesCervical cancerPrimary cell linesNeu expressionPrimary cervical cancer cell linesCell linesHER-2/neu expressionSite of recurrenceInhibition of proliferationEffector cellsMetastatic lesionsIL-2Primary treatmentTumor biopsiesCellular cytotoxicityHumanized mAbOriginal tumorRecurrent sitesLow dosesFlow cytometryLow expression