DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial
Iyer G, Tangen C, Sarfaty M, Regazzi A, Lee I, Fong M, Choi W, Dinney C, Flaig T, Thompson I, Lerner S, McConkey D, Rosenberg J. DNA Damage Response Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial. JCO Precision Oncology 2024, 8: e2400287. PMID: 39499893, DOI: 10.1200/po.24.00287.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCisplatinDNA DamageFemaleHumansMaleMiddle AgedNeoadjuvant TherapyNeoplasm InvasivenessUrinary Bladder NeoplasmsXeroderma Pigmentosum Group D ProteinConceptsNeoadjuvant cisplatin-based chemotherapyMuscle-invasive bladder cancerProgression-free survivalDDR alterationsDNA damage response alterationPathological responseBladder cancerDNA damage responseAssociated with pathological responseNeoadjuvant chemotherapy sensitivityPretreatment tumor specimensPathological response rateCisplatin-based chemotherapyDNA damage response genesEstimates of hazard ratiosOverall survivalRadical cystectomyTumor specimensPerformance statusClinical stageChemotherapy sensitivityCox regressionHazard ratioNext-generation sequencingPatientsMitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer
Reddy K, Piyarathna D, Park J, Putluri V, Amara C, Kamal A, Xu J, Kraushaar D, Huang S, Jung S, Eberlin L, Johnson J, Kittles R, Ballester L, Parsawar K, Siddiqui M, Gao J, Gramer A, Bollag R, Terris M, Lotan Y, Creighton C, Lerner S, Sreekumar A, Kaipparettu B, Putluri N. Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer. JCI Insight 2024, 9: e172336. PMID: 39253977, PMCID: PMC11385078, DOI: 10.1172/jci.insight.172336.Peer-Reviewed Original ResearchConceptsBladder cancerOxidative phosphorylationComponents of complex IComplex IElevated mitochondrial oxidative phosphorylationComprehensive RNA-seqReduced basal respirationActive oxidative phosphorylationMitochondrial oxidative phosphorylationDecreased tumor growthTumor growth potentialIncreased disease progressionMitochondrial respiration rateAfrican American patientsRNA-seqRace-specific differencesMitochondrial reprogrammingEuropean AmericansMetabolic rewiringOXPHOS activityBasal respirationGlutamine metabolismGLS1 expressionPreclinical studiesATP productionEfficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin–Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial
Narayan V, Boorjian S, Alemozaffar M, Konety B, Shore N, Gomella L, Kamat A, Bivalacqua T, Montgomery J, Lerner S, Busby J, Poch M, Crispen P, Steinberg G, Schuckman A, Downs T, Mashni J, Lane B, Guzzo T, Bratslavsky G, Karsh L, Woods M, Brown G, Canter D, Luchey A, Lotan Y, Inman B, Williams M, Cookson M, Chang S, Sankin A, O’Donnell M, Sawutz D, Philipson R, Parker N, Yla-Herttuala S, Rehm D, Jakobsen J, Juul K, Dinney C. Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin–Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial. Journal Of Urology 2024, 212: 74-86. PMID: 38704840, DOI: 10.1097/ju.0000000000004020.Peer-Reviewed Original ResearchConceptsNonmuscle-invasive bladder cancerPhase 3 trialBladder cancerFollow-upAdenoviral vector-based gene therapyProgression to muscle-invasive diseaseOpen-label phase 3 trialVector-based gene therapyCystectomy-free survivalMuscle-invasive diseaseMedian follow-upCarcinoma in situBladder preservationNadofaragene firadenovecOverall survivalGene therapyCytological assessmentTa/T1PatientsUS sitesCohortReceiving treatmentMonthsCancerHGRFThe IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer
Amara C, Kami Reddy K, Yuntao Y, Chan Y, Piyarathna D, Dobrolecki L, Shih D, Shi Z, Xu J, Huang S, Ellis M, Apolo A, Ballester L, Gao J, Hansel D, Lotan Y, Hodges H, Lerner S, Creighton C, Sreekumar A, Zheng W, Msaouel P, Kavuri S, Putluri N. The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer. Nature Communications 2024, 15: 1373. PMID: 38355560, PMCID: PMC10867091, DOI: 10.1038/s41467-024-45132-2.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorHumansInterleukin-6Signal TransductionSMARCB1 ProteinSTAT3 Transcription FactorUrinary Bladder NeoplasmsConceptsSignaling axisSMARCB1-deficient tumorsSMARCB1 deficiencyBladder cancerChromatin accessibilitySTAT3 inhibitorTumor growthSMARCB1 lossPatient-derived xenograft modelsCell line-derived xenograftsTherapeutic vulnerabilitiesTarget pathwaysReduced tumor growthIncreased tumor growthCell linesIn vivo modelsSTAT3Gene signatureSMARCB1TTI-101Solid tumorsXenograft modelClinical evaluationDisease progressionTumor