2024
Unmet needs in cervical cancer – can biological therapies plug the gap?
Greenman M, Chang Y, McNamara B, Mutlu L, Santin A. Unmet needs in cervical cancer – can biological therapies plug the gap? Expert Opinion On Biological Therapy 2024, 24: 995-1003. PMID: 39311611, DOI: 10.1080/14712598.2024.2408754.Peer-Reviewed Original ResearchBiologic therapyCervical cancerIntroduction of biologic therapiesManagement of cervical cancerImmune checkpoint inhibitorsIncreased overall survivalCurrent treatment recommendationsMultiple tumor typesAntibody-drug conjugatesCheckpoint inhibitorsOverall survivalRecurrent diseaseGynecologic malignanciesTreat malignanciesTumor typesClinical outcomesAngiogenesis inhibitorsBurden of casesTreatment recommendationsTherapyImprove current standardsAntitumor activityInadequate screeningCancerMalignancy
2023
Pembrolizumab with chemotherapy, with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer
McNamara B, Chang Y, Mutlu L, Harold J, Santin A. Pembrolizumab with chemotherapy, with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer. Expert Opinion On Biological Therapy 2023, 23: 227-233. PMID: 36800548, DOI: 10.1080/14712598.2023.2182679.Peer-Reviewed Original ResearchConceptsUse of pembrolizumabCervical cancerStandard chemotherapyMetastatic PD-L1Recurrent cervical cancerMetastatic cervical cancerNon-expressing tumorsVEGF therapyPD-L1Clinical efficacyGlobal morbidityPharmacologic propertiesChemotherapyPembrolizumabBevacizumabCancerRecurrentTreatmentTolerabilityFurther benefitImmunotherapyContraindicationsMorbidityEvidencePatients
2022
Advances in antibody-drug conjugates for gynecologic malignancies
Tymon-Rosario J, Gorman M, Richardson D, Washington C, Santin A. Advances in antibody-drug conjugates for gynecologic malignancies. Current Opinion In Obstetrics & Gynecology 2022, 35: 6-14. PMID: 36484278, DOI: 10.1097/gco.0000000000000838.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesOvarian cancer patientsGynecologic malignanciesCancer patientsPlatinum-resistant ovarian cancer patientsUse of ADCsOngoing phase 3 trialsRecurrent ovarian cancer patientsNovel antibody-drug conjugateReceptor-targeting antibodiesPhase 3 trialProgression-free survivalFirst U.S. FoodOngoing clinical trialsHER2/neuPersonalized cancer careTisotumab vedotinPrimary endpointCervical cancerGynecologic cancerCancer careClinical trialsMultiple tumorsCurrent evidenceDrug Administration
2021
Immunotherapy in Cervical Cancer
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD. Immunotherapy in Cervical Cancer. Current Oncology Reports 2021, 23: 61. PMID: 33852056, DOI: 10.1007/s11912-021-01052-8.Peer-Reviewed Original ResearchConceptsCervical cancerDifferent immune checkpoint inhibitorsPlatinum-based chemotherapy regimenTumor-infiltrating T lymphocytesPoly adenosine diphosphate ribose polymerase inhibitorsImmune checkpoint inhibitorsCombination therapy trialsCervical cancer patientsPositive cervical cancerNovel therapeutic modalitiesRibose polymerase inhibitorsAntibody-drug conjugatesCheckpoint inhibitorsChemotherapy regimenImmunotherapy studiesTherapeutic vaccinesInvestigative treatmentCancer patientsChemotherapy treatmentT lymphocytesTherapeutic modalitiesRecent FindingsThereTumor angiogenesis inhibitorTherapy trialsAngiogenesis inhibitors
2020
Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
Oaknin A, Friedman CF, Roman LD, D’Souza A, Brana I, Bidard F, Goldman J, Alvarez EA, Boni V, ElNaggar AC, Passalacqua R, T.M. K, Santin AD, Keyvanjah K, Xu F, Eli LD, Lalani AS, Bryce RP, Hyman DM, Meric-Bernstam F, Solit DB, Monk BJ. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecologic Oncology 2020, 159: 150-156. PMID: 32723675, PMCID: PMC8336424, DOI: 10.1016/j.ygyno.2020.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultDiarrheaFemaleHumansKaplan-Meier EstimateMiddle AgedMutationNauseaNeoplasm Recurrence, LocalProgression-Free SurvivalProtein Kinase InhibitorsQuinolinesReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsSeverity of Illness IndexUterine Cervical NeoplasmsConceptsProgression-free survivalClinical benefit rateObjective response rateCervical cancerOverall survivalHER2 mutationsBasket trialsMetastatic/recurrent cervical cancerAdvanced/recurrent diseaseMedian progression-free survivalCommon HER2 mutationsGrade 3 diarrheaGrade 4 eventsHER2-mutant cancersSafety of neratinibCommon adverse eventsMedian overall survivalRecurrent cervical cancerMetastatic cervical cancerNew safety signalsPhase II basket trialPlatinum-based treatmentTyrosine kinase inhibitorsWarrants further investigationEligible patientsNovel antibody-drug conjugates: current and future roles in gynecologic oncology.
Tymon-Rosario J, Zeybek B, Santin AD. Novel antibody-drug conjugates: current and future roles in gynecologic oncology. Current Opinion In Obstetrics & Gynecology 2020, 33: 26-33. PMID: 32618744, PMCID: PMC8253558, DOI: 10.1097/gco.0000000000000642.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesAntigen-negative cellsNovel antibody-drug conjugateAggressive gynecologic malignancyReceptor-targeting antibodiesTrop-2 overexpressionOngoing clinical trialsHER2/neuPersonalized cancer careNormal surrounding tissueAntigen-positive target cellsGynecologic malignanciesGynecologic tumorsCervical cancerSacituzumab govitecanCancer careGynecologic oncologyPreclinical dataTrastuzumab emtansineADC therapyClinical trialsMultiple tumorsCurrent standard practiceNoncleavable linkerCytotoxic moleculesPhase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)
Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecologic Oncology 2020, 157: 161-166. PMID: 31924334, PMCID: PMC7127981, DOI: 10.1016/j.ygyno.2019.12.034.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsRecurrent cervical cancerPD-L1 expressionPlatinum-based chemotherapyCervical cancerStable diseaseGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsGrade 5 treatment-related adverse eventsECOG PS 0Prior systemic therapyRecurrent cervical carcinomaResponse/toxicitySingle-agent nivolumabSystemic chemotherapy regimenTolerability of nivolumabImmune checkpoint inhibitorsPercent of patientsAcceptable safety profilePhase II trialKey eligibility criteriaPhase II evaluationECOG PSNivolumab 3RECIST 1.1
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsPARP-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 activityCervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan.
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Buza N, Lopez S, Perrone E, Manara P, Bellone S, Zammataro L, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Journal Of Clinical Oncology 2019, 37: e17028-e17028. DOI: 10.1200/jco.2019.37.15_suppl.e17028.Peer-Reviewed Original ResearchSquamous cell carcinomaPrimary cervical cancer cell linesControl antibody drug conjugatesAntibody-drug conjugatesIMMU-132Clear cell carcinomaTrop-2 expressionCervical cancer cell linesCell carcinomaCancer cell linesCervical cancerSacituzumab govitecanNeuroendocrine carcinomaCervical tumorsCell linesTrop-2Cervical cancer cell viabilityNaked antibodiesWeekly intravenous administrationSignificant tumor growth inhibitionStrong diffuse stainingUnmet medical needPrimary tumor cell linesReal-time polymerase chain reactionTumor growth inhibition
2018
280TiP GOG 3016/ENGOT-cx9: An open-label, multi-national, randomized, phase III trial of cemiplimab, an anti-PD-1, versus investigator's choice (IC) chemotherapy in ≥ second-line recurrent or metastatic cervical cancer
Tewari K, Vergote I, Oaknin A, Alvarez E, Gaillard S, Lheureux S, Rischin D, Santin A, Feng M, Mathias M, Fury M, Lowy I, Monk B. 280TiP GOG 3016/ENGOT-cx9: An open-label, multi-national, randomized, phase III trial of cemiplimab, an anti-PD-1, versus investigator's choice (IC) chemotherapy in ≥ second-line recurrent or metastatic cervical cancer. Annals Of Oncology 2018, 29: ix86. DOI: 10.1093/annonc/mdy436.027.Peer-Reviewed Original ResearchGOG 3016/ENGOT-cx9: An open-label, multi-national, randomized, phase 3 trial of cemiplimab, an anti-PD-1, versus investigator's choice (IC) chemotherapy in ≥2 line recurrent or metastatic cervical cancer.
Tewari K, Vergote I, Oaknin A, Alvarez E, Chase D, Gaillard S, Lheureux S, Rischin D, Santin A, Feng M, Mathias M, Fury M, Lowy I, Monk B. GOG 3016/ENGOT-cx9: An open-label, multi-national, randomized, phase 3 trial of cemiplimab, an anti-PD-1, versus investigator's choice (IC) chemotherapy in ≥2 line recurrent or metastatic cervical cancer. Journal Of Clinical Oncology 2018, 36: tps5600-tps5600. DOI: 10.1200/jco.2018.36.15_suppl.tps5600.Peer-Reviewed Original ResearchA phase II evaluation of nivolumab, a fully human antibody against PD-1, in the treatment of persistent or recurrent cervical cancer.
Santin A, Deng W, Frumovitz M, Huh W, Khleif S, Lankes H, Ratner E, O'Cearbhaill R, Jazaeri A, Birrer M. A phase II evaluation of nivolumab, a fully human antibody against PD-1, in the treatment of persistent or recurrent cervical cancer. Journal Of Clinical Oncology 2018, 36: 5536-5536. DOI: 10.1200/jco.2018.36.15_suppl.5536.Peer-Reviewed Original Research
2016
The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines
Bandiera E, Todeschini P, Romani C, Zanotti L, Erba E, Colmegna B, Bignotti E, Santin AD, Sartori E, Odicino FE, Pecorelli S, Tassi RA, Ravaggi A. The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines. Oncology Letters 2016, 12: 2493-2500. PMID: 27698818, PMCID: PMC5038480, DOI: 10.3892/ol.2016.5008.Peer-Reviewed Original ResearchCC cell linesCervical cancerCell linesCell proliferationHIV protease inhibitor saquinavirProteasomal activityActive antiretroviral therapyHuman immunodeficiency virusCell invasionDirect antitumor activityCervical cancer cell linesHIV protease inhibitorsAntiretroviral therapyCancer cell linesSaquinavir concentrationsImmunodeficiency virusPropidium iodide stainingInhibitor saquinavirMatrigel chamberAntineoplastic effectsInnovative therapiesClinical modelSaquinavirCytometric analysisTherapeutic agents
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 sequencingInhibitorsPrognosis
2014
Taxanes
Schwab CL, English DP, Roque DM, Santin AD. Taxanes. Anti-Cancer Drugs 2014, 25: 522-535. PMID: 24300913, PMCID: PMC3980024, DOI: 10.1097/cad.0000000000000057.Peer-Reviewed Original ResearchConceptsTaxane-based chemotherapyUse of taxanesGynecologic cancerRoute of treatmentRadiation sensitizing propertiesGynecologic malignanciesCervical cancerEffective therapyTreatment intervalAppropriate doseResponse rateNew treatmentsChemotherapeutic agentsTaxanesCancerSensitizing propertiesChemotherapyTreatmentActive agentsMalignancyDocetaxelOvarianTherapyAgentsDose
2012
Corrigendum to “The Significance of Perineural Invasion in Early-stage Cervical Cancer” [Gynecologic Oncology 123 (2011) 561–564]
ElSahwi K, Barber E, Illuzzi J, Buza N, Ratner E, Silasi D, Santin A, Azodi M, Schwartz P, Hui P, Rutherford T. Corrigendum to “The Significance of Perineural Invasion in Early-stage Cervical Cancer” [Gynecologic Oncology 123 (2011) 561–564]. Gynecologic Oncology 2012, 125: 770. DOI: 10.1016/j.ygyno.2012.02.026.Peer-Reviewed Original Research
2011
The significance of perineural invasion in early-stage cervical cancer
ElSahwi KS, Barber E, Illuzzi J, Buza N, Ratner E, Silasi DA, Santin AD, Azodi M, Schwartz PE, Rutherford TJ. The significance of perineural invasion in early-stage cervical cancer. Gynecologic Oncology 2011, 123: 561-564. PMID: 21968340, DOI: 10.1016/j.ygyno.2011.08.028.Peer-Reviewed Original ResearchConceptsEarly cervical cancerPerineural invasionCervical cancerRisk factorsAdjuvant therapyEarly-stage cervical cancer patientsEarly-stage cervical cancerMultiple high-risk factorsAdjusted hazard ratioIndependent risk factorRetrospective chart reviewLymphovascular space invasionCervical cancer patientsLarger tumor sizeHigh-risk factorsChart reviewHazard ratioCervical stromaParametrial invasionWorse prognosisPoor prognosisSpace invasionTumor sizeMean ageTumor extensionCervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. American Journal Of Obstetrics And Gynecology 2011, 205: 567.e1-567.e7. PMID: 21889762, PMCID: PMC3224189, DOI: 10.1016/j.ajog.2011.06.093.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntibodies, MonoclonalAntigens, NeoplasmBiomarkers, TumorCarcinoma, Squamous CellCell Adhesion MoleculesCell Line, TumorComplement System ProteinsDrug Resistance, NeoplasmDrug SynergismFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GInterleukin-2Killer Cells, NaturalReal-Time Polymerase Chain ReactionUterine Cervical NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityAnti-Trop-2 antibodyTrop-2 expressionReal-time polymerase chain reactionCell surface markersCervical cancerPolymerase chain reactionHighest messenger RNA expressionCell-dependent cytotoxicityCell-mediated cytotoxicityNovel treatment optionsChromium release assaysConventional treatment modalitiesChain reactionComplement-dependent cytotoxicityEffects of interleukinMessenger RNA expressionLevel of cytotoxicityCancer refractoryCervical carcinomaTreatment optionsTreatment modalitiesIL-2Normal cervixRelease assaysExpression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor
Cocco E, Varughese J, Buza N, Bellone S, Glasgow M, Bellone M, Todeschini P, Carrara L, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Lockwood CJ, Santin AD. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor. BMC Cancer 2011, 11: 263. PMID: 21693061, PMCID: PMC3141777, DOI: 10.1186/1471-2407-11-263.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCell Line, TumorComplement System ProteinsCytotoxicity Tests, ImmunologicDrug Screening Assays, AntitumorFemaleHuman papillomavirus 16Human papillomavirus 18HumansImmunoconjugatesImmunoglobulin GImmunotherapyInterleukin-2KeratinocytesMolecular Targeted TherapyNeoplasm ProteinsNeovascularization, PathologicPapillomavirus InfectionsRNA, MessengerRNA, NeoplasmThromboplastinUterine Cervical NeoplasmsConceptsCervical cancer cell linesPrimary cervical cancer cell linesCervical carcinoma cell linesCancer cell linesCervical cancerCarcinoma cell linesFactor VII/VIIaTissue factorUterine cervixCell linesImportant worldwide health problemTargeting tissue factorStandard treatment modalitySquamous cell carcinomaExpression of TFWorldwide health problemNovel therapeutic agentsNormal cervical keratinocytesAdenocarcinoma histologyBackgroundCervical cancerCancer refractoryRecurrent diseaseCell carcinomaTreatment modalitiesNovel therapies