2023
Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene AmplificationHumansLeiomyosarcomaMAP Kinase Kinase 4MiceMice, SCIDNeoplasm Recurrence, LocalPelvic NeoplasmsUterine NeoplasmsConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcoma
2021
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedDNA Mismatch RepairEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityNeoplasm Recurrence, LocalPilot ProjectsProspective StudiesConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIPrognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy
Li JY, Park HS, Huang GS, Young MR, Ratner E, Santin A, Damast S. Prognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy. Gynecologic Oncology 2021, 163: 557-562. PMID: 34602287, DOI: 10.1016/j.ygyno.2021.09.018.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalEndometrioid endometrial cancerVaginal brachytherapyPMMR patientsOverall survivalEEC patientsEndometrial cancerExact testThree-year recurrence-free survivalEarly-stage endometrial cancerCox proportional hazards regressionPoor recurrence-free survivalAdjuvant vaginal brachytherapyThree-year OSMultivariable Cox regressionLympho-vascular invasionSignificant prognostic variablesProportional hazards regressionLog-rank testKaplan-Meier estimatesDeficient mismatch repairMismatch repair statusFisher's exact testMismatch repair deficiencyDMMR statusTrastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu
Tymon-Rosario J, Siegel ER, Bellone S, Harold J, Adjei N, Zeybek B, Mauricio D, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Azodi M, Schwartz PE, Fader AN, Santin AD. Trastuzumab tolerability in the treatment of advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress HER2/neu. Gynecologic Oncology 2021, 163: 93-99. PMID: 34372971, PMCID: PMC8721852, DOI: 10.1016/j.ygyno.2021.07.033.Peer-Reviewed Original ResearchMeSH KeywordsAgedCystadenocarcinoma, SerousFemaleHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingReceptor, ErbB-2TrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaRecurrent uterine serous carcinomaAdverse eventsTreatment armsSerous carcinomaExperimental armToxicity profileTreatment-related adverse eventsTrastuzumab maintenance therapyCarboplatin/paclitaxelCardiac adverse eventsEndometrial cancer patientsGastrointestinal adverse eventsManageable toxicity profilePhase II trialEfficacy of trastuzumabSystem organ classII trialMaintenance therapyPrimary endpointSecondary endpointsMaintenance treatmentSafety profileCancer patientsCumulative toxicityA phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793)
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon-Rosario J, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin AD. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Annals Of Oncology 2021, 32: 1045-1046. PMID: 33932502, PMCID: PMC9465821, DOI: 10.1016/j.annonc.2021.04.013.Commentaries, Editorials and LettersSex Hormones, Insulin, and Insulin-like Growth Factors in Recurrence of High-Stage Endometrial CancerSex Hormones and Insulin in Endometrial Cancer Recurrence
Merritt MA, Strickler HD, Hutson AD, Einstein MH, Rohan TE, Xue X, Sherman ME, Brinton LA, Yu H, Miller DS, Ramirez NC, Lankes HA, Birrer MJ, Huang GS, Gunter MJ. Sex Hormones, Insulin, and Insulin-like Growth Factors in Recurrence of High-Stage Endometrial CancerSex Hormones and Insulin in Endometrial Cancer Recurrence. Cancer Epidemiology Biomarkers & Prevention 2021, 30: 719-726. PMID: 33622671, PMCID: PMC8026669, DOI: 10.1158/1055-9965.epi-20-1613.Peer-Reviewed Original ResearchConceptsEndometrial cancer recurrenceSex hormonesEndometrial cancerProgesterone receptorCancer recurrenceInsulin/insulin-like growth factor axisRecurrence riskInsulin-like growth factor (IGF) axisInsulin-like growth factorGynecologic Oncology GroupProgression-free survivalEndometrial adenocarcinoma patientsIGF-binding proteinsFuture clinical trialsGrowth factor axisConfidence intervalsIR/IGF1RAdjuvant therapyER positivityIGFBP-3Oncology GroupProspective cohortAdenocarcinoma patientsPretreatment specimensSerum concentrations
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
2015
The impact of obesity on prostate cancer recurrence observed after exclusion of diabetics
Agalliu I, Williams S, Adler B, Androga L, Siev M, Lin J, Xue X, Huang G, Strickler HD, Ghavamian R. The impact of obesity on prostate cancer recurrence observed after exclusion of diabetics. Cancer Causes & Control 2015, 26: 821-830. PMID: 25771797, PMCID: PMC4984400, DOI: 10.1007/s10552-015-0554-z.Peer-Reviewed Original ResearchMeSH KeywordsAgedBody Mass IndexDiabetes Mellitus, Type 2HumansMaleMiddle AgedNeoplasm Recurrence, LocalObesityProstatectomyProstate-Specific AntigenProstatic NeoplasmsRetrospective StudiesConceptsBody mass indexBMI/obesityProstate cancer recurrenceCancer recurrencePRCA patientsBeta-cell insulin productionCox proportional hazards modelExclusion of diabeticsAnti-diabetes medicationsImpact of obesityNormal-weight menPathological tumor characteristicsType 2 diabetesProportional hazards modelObese menSerum PSAAdvanced diabetesMass indexTumor characteristicsWeight menRadical prostatectomyObesity associationRecurrence eventsHazards modelObesity
2011
Performance of Serum CA125 as a Prognostic Biomarker in Patients With Uterine Papillary Serous Carcinoma
Gupta D, Gunter MJ, Yang K, Lee S, Zuckerwise L, Chen LM, Goldberg GL, Huang GS. Performance of Serum CA125 as a Prognostic Biomarker in Patients With Uterine Papillary Serous Carcinoma. International Journal Of Gynecological Cancer 2011, 21: 529-534. PMID: 21436701, DOI: 10.1097/igc.0b013e31821091b5.Peer-Reviewed Original ResearchConceptsUterine papillary serous carcinomaPapillary serous carcinomaCA125 levelsLymph node metastasisDisease recurrenceCA125 elevationMetastatic diseaseNode metastasisSerum CA125Serous carcinomaStage III/IV diseaseCox proportional hazards regression modelingProportional hazards regression modelingElevated CA125 levelsPreoperative CA125 levelsLymph node involvementRecurrence-free survivalAdvanced International FederationMultivariate survival analysisUPSC patientsMean followSurgical stagingCA125 measurementNode involvementIndependent predictors