2023
Elimusertib has anti-tumor activity in preclinical patient-derived pediatric solid tumor models
Pusch F, García H, Xu R, Gürgen D, Bei Y, Brückner L, Röefzaad C, von Stebut J, Bardinet V, Gonzalez R, Eggert A, Schulte J, Hundsdörfer P, Seifert G, Haase K, Schäfer B, Wachtel M, Kühl A, Ortiz M, Wengner A, Scheer M, Henssen A. Elimusertib has anti-tumor activity in preclinical patient-derived pediatric solid tumor models. Molecular Cancer Therapeutics 2023, 23: 507-519. PMID: 38159110, PMCID: PMC10985474, DOI: 10.1158/1535-7163.mct-23-0094.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsPediatric solid tumor modelsPreclinical antitumor activitySolid tumor modelsTumor modelStandard-of-care chemotherapyAntitumor activityInhibitor of ataxia telangiectasiaSolid tumor entitiesClinically meaningful responseAnti-tumor activityPreclinical activityRad3-related proteinTumor entitiesPediatric malignanciesAntitumor effectCancer entitiesResponse biomarkersSmall molecule inhibitorsClinical trialsElimusertibMeaningful responseAtaxia telangiectasiaResponse rateCell lines
2022
Therapeutic targeting of ATR in alveolar rhabdomyosarcoma
Dorado García H, Pusch F, Bei Y, von Stebut J, Ibáñez G, Guillan K, Imami K, Gürgen D, Rolff J, Helmsauer K, Meyer-Liesener S, Timme N, Bardinet V, Chamorro González R, MacArthur I, Chen C, Schulz J, Wengner A, Furth C, Lala B, Eggert A, Seifert G, Hundsoerfer P, Kirchner M, Mertins P, Selbach M, Lissat A, Dubois F, Horst D, Schulte J, Spuler S, You D, Dela Cruz F, Kung A, Haase K, DiVirgilio M, Scheer M, Ortiz M, Henssen A. Therapeutic targeting of ATR in alveolar rhabdomyosarcoma. Nature Communications 2022, 13: 4297. PMID: 35879366, PMCID: PMC9314382, DOI: 10.1038/s41467-022-32023-7.Peer-Reviewed Original ResearchConceptsCRISPR activation screenAlveolar rhabdomyosarcomaATR inhibitionGenome-wide CRISPR activation screenClinical outcomes of patientsMulti-modal treatment approachSensitivity to ATR inhibitionOutcomes of patientsPAX3-FOXO1Rad3 related proteinMuscle progenitor cellsDNA repair pathway activityClinical outcomesInhibition in vitroATR inhibitorsProgenitor cellsClinical trialsBRCA1 phosphorylationRas-MAPK pathwayCombined treatmentARMS cellsPARP1 inhibitorsAtaxia telangiectasiaRhabdomyosarcoma cellsTreatment approaches
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