2024
The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1
Romero R, Chu T, González Robles T, Smith P, Xie Y, Kaur H, Yoder S, Zhao H, Mao C, Kang W, Pulina M, Lawrence K, Gopalan A, Zaidi S, Yoo K, Choi J, Fan N, Gerstner O, Karthaus W, DeStanchina E, Ruggles K, Westcott P, Chaligné R, Pe’er D, Sawyers C. The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1. Nature Cancer 2024, 5: 1641-1659. PMID: 39394434, PMCID: PMC11584404, DOI: 10.1038/s43018-024-00838-6.Peer-Reviewed Original ResearchConceptsNeuroendocrine prostate cancerProstate cancerLineage plasticityAndrogen receptor signaling inhibitorsCancer progressionMouse prostate organoidsProstate cancer progressionRB1 deletionProstate organoidsMultiplex immunofluorescenceIn vivo platformTransient regressionDriver mutationsLuminal cellsSignaling inhibitorsAscl1Neuroendocrine transitionLineage transformationOrganoid culturesCancerTherapy outcomeProstateAdenocarcinomaTherapy timeIn vivo microenvironment
2023
2233MO CDC7 inhibition constrains lineage plasticity and prevents resistance and neuroendocrine transformation in the lung and prostate
Quintanal-Villalonga Á, Zaidi S, Karthaus W, Zhan Y, Shafer M, Qiu J, de Stanchina E, Haffner M, Sawyers C, Rudin C. 2233MO CDC7 inhibition constrains lineage plasticity and prevents resistance and neuroendocrine transformation in the lung and prostate. Annals Of Oncology 2023, 34: s1150. DOI: 10.1016/j.annonc.2023.09.1261.Peer-Reviewed Original ResearchExportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers
Quintanal-Villalonga A, Durani V, Sabet A, Redin E, Kawasaki K, Shafer M, Karthaus W, Zaidi S, Zhan Y, Manoj P, Sridhar H, Shah N, Chow A, Bhanot U, Linkov I, Asher M, Yu H, Qiu J, de Stanchina E, Patel R, Morrissey C, Haffner M, Koche R, Sawyers C, Rudin C. Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers. Science Translational Medicine 2023, 15: eadf7006. PMID: 37531417, PMCID: PMC10777207, DOI: 10.1126/scitranslmed.adf7006.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsProstatic adenocarcinomaNE transformationXenograft modelExportin 1Associated with poor prognosisProstate adenocarcinoma cell lineInactivation of TP53Adenocarcinoma xenograft modelEctopic SOX2 expressionEGFR inhibitor osimertinibAdenocarcinoma cell lineNE phenotypeNeuroendocrine transformationSelinexor treatmentStandard cytotoxicsProstate cancerLineage plasticityPotential therapeutic targetNE featuresPoor prognosisProstateSOX2 expressionAdenocarcinomaLungEffect of Janus kinase (JAK) signaling inhibition on lineage plasticity and drug sensitivity in castrate resistant prostate cancer.
Zaidi S, Chan J, Love J, Zhao J, Setty M, Lawrence K, Gopalan A, Goodrich D, Morris M, Chen Y, Karthaus W, Pe'er D, Sawyers C. Effect of Janus kinase (JAK) signaling inhibition on lineage plasticity and drug sensitivity in castrate resistant prostate cancer. Journal Of Clinical Oncology 2023, 41: 227-227. DOI: 10.1200/jco.2023.41.6_suppl.227.Peer-Reviewed Original ResearchAndrogen receptor signaling inhibitorsFDA-approved inhibitorFibroblast growth factor receptorLineage plasticityProstate cancerAndrogen receptorInhibitors of JAK/STATSuccess of targeted cancer therapyCastration resistant prostate cancerSignaling inhibitorsLoss of tumor suppressor genesCases of prostate cancerFibroblast growth factor receptor signaling pathwayJanus kinaseSingle cell RNA analysisRadiologically guided biopsyResistant prostate cancerEffects of Janus kinaseIncreased androgen receptorTumor-derived organoidsGenetic editing toolsResistance to therapySingle cell RNA sequencingGrowth factor receptorTumor suppressor gene
2022
Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling
Chan J, Zaidi S, Love J, Zhao J, Setty M, Wadosky K, Gopalan A, Choo Z, Persad S, Choi J, LaClair J, Lawrence K, Chaudhary O, Xu T, Masilionis I, Linkov I, Wang S, Lee C, Barlas A, Morris M, Mazutis L, Chaligne R, Chen Y, Goodrich D, Karthaus W, Pe'er D, Sawyers C. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling. Science 2022, 377: 1180-1191. PMID: 35981096, PMCID: PMC9653178, DOI: 10.1126/science.abn0478.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorProstate cancerLineage plasticityJanus kinaseGenetically engineered mouse modelsCastration-resistant diseaseFibroblast growth factor receptor signalingTumor cell statesGrowth factor receptorSingle-cell analysisMetastatic diseaseStratify patientsIncreased JAK/STATAntiandrogen resistanceEpithelial populationsDrug resistanceFactor receptorClinical trialsInhibitor treatmentMouse modelInflammatory signalingGene expressionCell statesMurine organoidsMolecular mechanisms
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