2023
Uterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315)
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, 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, Schlessinger J, Santin A. Uterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315). Gynecologic Oncology 2023, 176: s193. DOI: 10.1016/j.ygyno.2023.06.218.Peer-Reviewed Original ResearchUterine leiomyosarcomaGene amplificationUterine 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 ResearchConceptsUterine 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
2022
Elimusertib (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 vehicle