2024
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 ResearchConceptsNeoadjuvant 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 sequencingPatientsCirculating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer
Goldkorn A, Tangen C, Plets M, Bsteh D, Xu T, Pinski J, Ingles S, Triche T, MacVicar G, Vaena D, Crispino A, McConkey D, Lara P, Hussain M, Quinn D, Dorff T, Lerner S, Thompson I, Agarwal N. Circulating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer. JAMA Network Open 2024, 7: e2437871. PMID: 39374015, PMCID: PMC11581504, DOI: 10.1001/jamanetworkopen.2024.37871.Peer-Reviewed Original ResearchConceptsMetastatic hormone-sensitive prostate cancerMetastatic castration-resistant prostate cancerCirculating tumor cell countCirculating tumor cellsHormone-sensitive prostate cancerTumor cell countOverall survivalProstate cancerPrognostic valueCTC countsPrognostic factorsProgression to metastatic castration-resistant prostate cancerDiagnosed mHSPCPeripheral blood circulating tumor cellsClinical trialsBlood circulating tumor cellsCastration-resistant prostate cancerPrognostic studyCell countBaseline CTC countProgression-free survivalLines of therapyEnhanced overall survivalProstate-specific antigenIncreased prognostic valueMitochondrial 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 productionAdjuvant Everolimus in Non–Clear Cell Renal Cell Carcinoma
Gulati S, Tangen C, Ryan C, Vaishampayan U, Shuch B, Barata P, Pruthi D, Bergerot C, Tripathi A, Lerner S, Thompson I, Lara P, Pal S. Adjuvant Everolimus in Non–Clear Cell Renal Cell Carcinoma. JAMA Network Open 2024, 7: e2425288. PMID: 39106067, PMCID: PMC11304111, DOI: 10.1001/jamanetworkopen.2024.25288.Peer-Reviewed Original ResearchConceptsChromophobe renal cell carcinomaRecurrence-free survivalPapillary renal cell carcinomaRenal cell carcinomaNon-clear cell renal cell carcinomaResected renal cell carcinomaCell renal cell carcinomaOverall survivalWeeks of treatmentCell carcinomaAdverse eventsClinical trialsHazard ratioPhase 3 randomized clinical trialWeeks of everolimusHigher adverse eventsRate of adverse eventsIntermediate-high riskIntervention groupVery-high-riskCox regression modelsPotential treatment benefitsClinical trial dataTreatment-naivePartial nephrectomyBone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer
Gebrael G, Jo Y, Swami U, Plets M, Chehade C, Narang A, Gupta S, Myint Z, Sayegh N, Tangen C, Hussain M, Dorff T, Lara P, Lerner S, Thompson I, Agarwal N. Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer. JAMA Network Open 2024, 7: e2419966. PMID: 38980676, PMCID: PMC11234233, DOI: 10.1001/jamanetworkopen.2024.19966.Peer-Reviewed Original ResearchConceptsProgression-free survivalAndrogen deprivation therapyProstate-specific antigenHormone-sensitive prostate cancerBone painOverall survivalPost hoc secondary analysisProstate cancerSurvival outcomesPain statusAssociated with shorter progression-free survivalClinical trialsPresence of bone painProstate-specific antigen levelAssociated with worse overall survivalCastration-resistant prostate cancerShorter progression-free survivalIntention-to-treat populationSecondary analysisZubrod performance statusHigh-volume diseaseCompare survival outcomesCox proportional hazards regression modelsSecondary end pointsProportional hazards regression modelsEfficacy 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 ResearchConceptsSignaling 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
2023
Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses
DiNardo A, Arditi M, Kamat A, Koster K, Carrero S, Nishiguchi T, Lebedev M, Benjamin A, Avalos P, Lozano M, Moule M, McCune B, Herron B, Ladki M, Sheikh D, Spears M, Herrejon I, Dodge C, Kumar S, Hutchison R, Ofili T, Opperman L, Bernard J, Lerner S, Udeani G, Neal G, Netea M, Cirillo J. Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses. Trials 2023, 24: 636. PMID: 37794431, PMCID: PMC10548680, DOI: 10.1186/s13063-023-07662-w.Peer-Reviewed Original ResearchConceptsBacillus Calmette-GuerinBacillus Calmette-Guerin vaccineSARS-CoV-2 infectionRandomized controlled trialsSARS-CoV-2BCG vaccinationClinical course of SARS-CoV-2 infectionCourse of SARS-CoV-2 infectionTreatment groupsAdministration of BCG vaccineKaplan-Meier curvesCox proportional hazards modelsEffect of BCG vaccinationInfection in vitroInfection of healthcare workersEvidence of SARS-CoV-2 infectionHealthcare workersMulti-center randomized controlled trialProportional hazards modelImmunological markersIntradermal administrationHazard ratioNon-specific effectsImmune responseHigh risk