2023
HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma
McNamara B, Mutlu L, Greenman M, Harold J, Santin A. HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma. Cancers 2023, 15: 4085. PMID: 37627113, PMCID: PMC10452357, DOI: 10.3390/cancers15164085.Peer-Reviewed Original ResearchUterine serous carcinomaHuman epidermal growth factor receptor 2Uterine carcinosarcomaSerous carcinomaTraditional platinum-based chemotherapyEpidermal growth factor receptor 2Growth factor receptor 2Platinum-based chemotherapyOngoing clinical trialsRare histologic variantHER2 protein overexpressionAggressive metastatic potentialFactor receptor 2Distinct molecular profilesPreclinical evidenceUterine carcinomaHistologic variantsClinical trialsHER2 oncogeneReceptor 2Metastatic potentialCarcinomaMolecular profileMolecular targetsProtein overexpression
2020
Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study
Erickson BK, Najjar O, Damast S, Blakaj A, Tymon-Rosario J, Shahi M, Santin A, Klein M, Dolan M, Cimino-Mathews A, Buza N, Ferriss JS, Stone RL, Khalifa M, Fader AN. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study. Gynecologic Oncology 2020, 159: 17-22. PMID: 32709539, PMCID: PMC7541557, DOI: 10.1016/j.ygyno.2020.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemoradiotherapy, AdjuvantCystadenocarcinoma, SerousFemaleFollow-Up StudiesHumansHysterectomyImmunohistochemistryMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingPrognosisProgression-Free SurvivalReceptor, ErbB-2Retrospective StudiesRisk AssessmentUnited StatesUterine NeoplasmsUterusConceptsHuman epidermal growth factor 2Uterine serous carcinomaHER2-positive tumorsEarly-stage diseaseOverall survivalSerous carcinomaCohort studyHER2 positivityPositive tumorsEarly stage uterine serous carcinomaLymph-vascular space invasionRecurrent uterine serous carcinomaMulti-institutional cohort studyHuman epidermal growth factor receptor 2Multi-center cohort studyEpidermal growth factor receptor 2Epidermal growth factor 2HER2-positive cohortGrowth factor receptor 2HER2-negative tumorsEquivocal IHC resultsFactor receptor 2Inferior PFSAdjuvant therapyGrowth factor 2Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies.
Erickson BK, Zeybek B, Santin AD, Fader AN. Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2020, 32: 57-64. PMID: 31833974, PMCID: PMC7307693, DOI: 10.1097/gco.0000000000000599.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Uterine serous carcinomaGynecologic malignanciesFactor receptor 2Serous carcinomaReceptor 2Recurrent uterine serous carcinomaAnti-HER2 antibody trastuzumabHER2-positive diseaseAnti-HER2 therapyAnti-HER2 treatmentHER2-positive breastTrial of womenEndometrial cancer subtypesMore treatment optionsEffective therapeutic targetTreatment optionsUterine carcinosarcomaTrastuzumab efficacyHER2 amplificationTargeted therapyGastric cancerSignificant efficacy
2018
Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Journal Of Clinical Oncology 2018, 36: 2044-2051. PMID: 29584549, DOI: 10.1200/jco.2017.76.5966.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Progression-free survivalUterine serous carcinomaRecurrent uterine serous carcinomaMedian progression-free survivalRandomized phase II trialEpidermal growth factor receptor 2Phase II trialGrowth factor receptor 2Serous carcinomaHER2/neuFactor receptor 2II trialTreatment armsReceptor 2Stage IIIHER2/neu-positive diseaseOne-sided log-rank testMethods Eligible patientsPrimary end pointPrimary stage IIIUnexpected safety signalsLog-rank testHumanized monoclonal antibodyEligible patients
2015
Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro
Zhu L, Lopez S, Bellone S, Black J, Cocco E, Zigras T, Predolini F, Bonazzoli E, Bussi B, Stuhmer Z, Schwab CL, English DP, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro. Tumor Biology 2015, 36: 5505-5513. PMID: 25669172, PMCID: PMC5573583, DOI: 10.1007/s13277-015-3218-4.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaReceptor tyrosine kinase inhibitorsHER2/neu gene amplificationTyrosine kinase inhibitorsUSC cell linesNeu gene amplificationEndometrial cancerIrreversible pan-ErbB receptor tyrosine kinase inhibitorEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsEpidermal growth factor receptor 2Cell linesKinase inhibitorsEffect of dacomitinibStandard salvage chemotherapyGrowth factor receptor 2Serous endometrial cancerFlow cytometry-based assayHER2/neuFactor receptor 2Dose-dependent declineGene amplificationCell cycle distributionCytometry-based assayGrowth inhibition
2014
T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Medicine 2014, 3: 1256-1265. PMID: 24890382, PMCID: PMC4302675, DOI: 10.1002/cam4.274.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAged, 80 and overAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsApoptosisCarcinomaCell Cycle CheckpointsCell ProliferationDisease Models, AnimalFemaleGene AmplificationGene ExpressionGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMaytansineMiddle AgedReceptor, ErbB-2RNA, MessengerTrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesNovel antibody-drug conjugateT-DM1USC xenograftsAntibody-drug conjugatesSerous carcinomaAntibody-dependent cell-mediated cytotoxicityEpidermal growth factor receptor 2Cell linesPrimary USC cell linesGrowth factor receptor 2Cell-mediated cytotoxicityChromium release assaysNovel treatment optionsHER2 protein overexpressionFactor receptor 2HER2 gene amplificationHER2 protein expressionC-erbB2 gene amplificationGene amplificationDisease refractoryPrimary HER2USC cellsUSC patients