2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, 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, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicleLenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, McCormack M, Smith A, Keefe S, Bird S, Dutta L, Orlowski R, Lorusso D. Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer. Obstetrical & Gynecological Survey 2022, 77: 275-276. DOI: 10.1097/ogx.0000000000001032.Peer-Reviewed Original ResearchEndometrial cancerRecurrent endometrial cancerSecond-line treatmentAdvanced endometrial cancerPlatinum-based chemotherapyRecurrent endometrial carcinomaTyrosine kinase inhibitorsEndometrial carcinomaOptimal treatmentDisease progressionLimited efficacySingle agentKinase inhibitorsLenvatinibCancerTreatmentPembrolizumabLittle consensusChemotherapyCarcinomaProgression
2020
Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts
Kim K, Hu W, Audenet F, Almassi N, Hanrahan AJ, Murray K, Bagrodia A, Wong N, Clinton TN, Dason S, Mohan V, Jebiwott S, Nagar K, Gao J, Penson A, Hughes C, Gordon B, Chen Z, Dong Y, Watson PA, Alvim R, Elzein A, Gao SP, Cocco E, Santin AD, Ostrovnaya I, Hsieh JJ, Sagi I, Pietzak EJ, Hakimi AA, Rosenberg JE, Iyer G, Vargas HA, Scaltriti M, Al-Ahmadie H, Solit DB, Coleman JA. Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts. Nature Communications 2020, 11: 1975. PMID: 32332851, PMCID: PMC7181640, DOI: 10.1038/s41467-020-15885-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiopsyCamptothecinCarcinoma, Transitional CellFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic VariationHigh-Throughput Nucleotide SequencingHumansImmunoconjugatesInterleukin Receptor Common gamma SubunitMaleMiceMice, Inbred NODMice, SCIDMiddle AgedMutationNeoplasm MetastasisNeoplasm TransplantationPhenotypePrecision MedicineProspective StudiesQuinolinesRetrospective StudiesSequence Analysis, RNATrastuzumabUrinary Bladder NeoplasmsUrotheliumConceptsUpper tract urothelial carcinomaUrothelial carcinomaCorresponding patient tumorsEstablishment of patientHigh genomic concordancePersonalized medicine strategiesHER2 kinase inhibitorDisease-specific modelsUTUC patientsCell line modelsPDX modelsBladder cancerTreatment paradigmGenomic concordanceInvasive tumorsSuperior efficacyPatient tumorsPatientsKinase inhibitorsAntibody drugsMedicine strategiesBiological heterogeneityCarcinomaXenograftsTumors
2018
Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it.
Menderes G, Lopez S, Han C, Altwerger G, Gysler S, Varughese J, Schwartz PE, Santin AD. Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it. Discovery Medicine 2018, 26: 39-50. PMID: 30265854.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaTyrosine kinase inhibitorsUSC patientsSerous carcinomaHER2/neu-targeted therapiesEndometrial cancer-related deathsHER2/neu amplificationKinase inhibitorsSingle-agent trastuzumabSignificant clinical activityRecent whole-exome sequencing studiesCancer-related deathEffective therapeutic strategyTumor growth inhibitionEndometrial cancerAggressive subtypeMechanisms of resistanceWhole-exome sequencing studiesClinical activityPreclinical studiesTarget therapyTherapeutic strategiesNeu amplificationHER2Therapy
2015
Immunotherapy and targeted therapy for cervical cancer: an update
Menderes G, Black J, Schwab CL, Santin AD. Immunotherapy and targeted therapy for cervical cancer: an update. Expert Review Of Anticancer Therapy 2015, 16: 83-98. PMID: 26568261, DOI: 10.1586/14737140.2016.1121108.Peer-Reviewed Original ResearchConceptsCervical cancer patientsCervical cancerCancer patientsImmune check pointsUse of immunotherapyMetastatic cervical cancerPrognosis of patientsActionable driver mutationsTyrosine kinase inhibitorsImmune system interactionsImmunotherapy studiesMedian survivalAngiogenesis inhibitorsChemotherapeutic drugsPatientsDriver mutationsKinase inhibitorsNew therapeuticsCancerNext-generation sequencingImmunotherapyTherapyGeneration sequencingInhibitorsPrognosisNeratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo
Schwab C, English D, Black J, Lopez S, Bellone S, Roque D, Ratner E, Silasi D, Azodi M, Rutherford T, Schwartz P, Santin A. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo. Gynecologic Oncology 2015, 137: 61. DOI: 10.1016/j.ygyno.2015.01.142.Peer-Reviewed Original ResearchDacomitinib (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 inhibitionHER2 as Biomarker for Endometrial Cancer
English D, Roque D, Buza N, Santin A. HER2 as Biomarker for Endometrial Cancer. Biomarkers In Disease: Methods, Discoveries And Applications 2015, 507-526. DOI: 10.1007/978-94-007-7681-4_26.ChaptersEndometrial cancerEpidermal growth factor (EGF) familyGrowth factor familyC-erbB2 geneFactor familyCell survivalErbB pathwayNovel tyrosine kinase inhibitorOverall poor survivalOverexpression of HER2Tyrosine kinase inhibitorsKinase inhibitorsEndometrial neoplasmsPoor survivalPathwayTumor typesHER2Monoclonal antibodiesCancerGenesBiomarkersOverexpressionSurvivalWide varietyErbB2
2014
HER2 as Biomarker for Endometrial Cancer
English D, Roque D, Buza N, Santin A. HER2 as Biomarker for Endometrial Cancer. 2014, 1-16. DOI: 10.1007/978-94-007-7744-6_26-1.ChaptersEndometrial cancerEpidermal growth factor (EGF) familyGrowth factor familyC-erbB2 geneFactor familyCell survivalErbB pathwayNovel tyrosine kinase inhibitorOverall poor survivalOverexpression of HER2Tyrosine kinase inhibitorsKinase inhibitorsEndometrial neoplasmsPoor survivalPathwayTumor typesHER2Monoclonal antibodiesCancerGenesBiomarkersOverexpressionSurvivalWide varietyErbB2
2013
HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies
English DP, Roque DM, Santin AD. HER2 Expression Beyond Breast Cancer: Therapeutic Implications for Gynecologic Malignancies. Molecular Diagnosis & Therapy 2013, 17: 85-99. PMID: 23529353, PMCID: PMC3660991, DOI: 10.1007/s40291-013-0024-9.Peer-Reviewed Original ResearchConceptsAggressive neoplasmCytotoxic chemotherapy agentsOverall poor survivalTyrosine kinase inhibitorsEpidermal growth factor (EGF) familyGrowth factor familyGynecologic malignanciesEndometrial cancerHER2 expressionClinical trialsOvarian cancerPoor survivalBreast cancerChemotherapy agentsC-erbB2 geneTherapeutic implicationsTumor typesHER2Monoclonal antibodiesSubset of breastKinase inhibitorsCancerNeoplasmsCell survivalBreast