2025
Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge
Qin T, Mattox A, Campbell J, Park J, Shin K, Li S, Sadow P, Faquin W, Micevic G, Daniels A, Haddad R, Garris C, Pittet M, Mempel T, ONeill A, Sartor M, Pai S. Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge. Journal Of Clinical Investigation 2025, 135: e181671. PMID: 40091844, PMCID: PMC11910227, DOI: 10.1172/jci181671.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsAzacitidineB7-H1 AntigenEpigenesis, GeneticFemaleHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsImmunotherapyMaleMiddle AgedProgrammed Cell Death 1 ReceptorSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentConceptsHead and neck squamous cell carcinomaTumor microenvironmentProlonged OSOverall survivalIFN-gCD8+ T cell infiltrationCD4+ T regulatory cellsOn-treatment tumor biopsiesNeck squamous cell carcinomaSystemic host immune responseBackgroundImmune checkpoint blockadeMetastatic (R/MMedian overall survivalPD-L1 expressionT cell infiltrationLocal tumor microenvironmentT regulatory cellsSquamous cell carcinomaBiologically effective dosePhase 1b clinical trialHost immune responseCheckpoint blockadeOS ratesPD-L1Tumor biopsiesTop advances of the year: Small cell lung cancer
Shields M, Chiang A, Byers L. Top advances of the year: Small cell lung cancer. Cancer 2025, 131: e35770. PMID: 40040254, DOI: 10.1002/cncr.35770.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerExtensive-stage small cell lung cancerCell lung cancerLung cancerLimited-stage small cell lung cancerFrequency of disease relapseTiming of immunotherapyCancer-related mortalityLong-term survivalAntibody-drug conjugatesNeuroendocrine subtypeDisease relapseAggressive biologyMetastatic spreadInferior outcomesImproved survivalImmunotherapyTherapeutic breakthroughConsolidation treatmentCancerPrecision medicineBiomarker selectionSurvivalLurbinectedinForward-thinking approachProceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation
Morris Z, Demaria S, Monjazeb A, Formenti S, Weichselbaum R, Welsh J, Enderling H, Schoenfeld J, Brody J, McGee H, Mondini M, Kent M, Young K, Galluzzi L, Karam S, Theelen W, Chang J, Huynh M, Daib A, Pitroda S, Chung C, Serre R, Grassberger C, Deng J, Sodji Q, Nguyen A, Patel R, Krebs S, Kalbasi A, Kerr C, Vanpouille-Box C, Vick L, Aguilera T, Ong I, Herrera F, Menon H, Smart D, Ahmed J, Gartrell R, Roland C, Fekrmandi F, Chakraborty B, Bent E, Berg T, Hutson A, Khleif S, Sikora A, Fong L. Proceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation. The Lancet Oncology 2025, 26: e152-e170. PMID: 40049206, DOI: 10.1016/s1470-2045(24)00656-9.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseDelivery of radiotherapyTumor immune recognitionSelection of immunotherapyBiomarker-guided approachesNational Cancer Institute workshopClinical trial dataImmunotherapy combinationsClinical responseImprove patient outcomesPreclinical modelsPatient selectionRadiotherapyImmunotherapyClinical endpointsClinical dataClinical studiesImmune recognitionImmune responseImmune effectsAnimal studiesClinical translationPatient outcomesTrial dataNegative trialsFAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma
Lubrano S, Cervantes-Villagrana R, Faraji F, Ramirez S, Sato K, Adame-Garcia S, Officer A, Arang N, Rigiracciolo D, Anguiano Quiroz P, Martini C, Wang Y, Ferguson F, Bacchiocchi A, Halaban R, Coma S, Holmen S, Pachter J, Aplin A, Gutkind J. FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma. Cancer Cell 2025, 43: 428-445.e6. PMID: 40020669, PMCID: PMC11903146, DOI: 10.1016/j.ccell.2025.02.001.Peer-Reviewed Original ResearchConceptsBRAF V600E melanomaFocal adhesion kinaseV600E melanomaFAK inhibitorActivated focal adhesion kinaseFocal adhesion kinase inhibitionRaf-MEKActivation of focal adhesion signalingFocal adhesion kinase inhibitorResistance to BRAFiSyngeneic mouse modelMAPK pathway inhibitionFocal adhesion signalingPro-apoptotic activityMelanoma patientsAdhesion signalingImmune therapyBRAF mutationsBRAFiTranscriptome analysisMelanomaMouse modelPathway inhibitionBRAFMelanoma cellsAn antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy
Schrank B, Wang Y, Wu A, Tran N, Lee D, Edwards J, Huntoon K, Dong S, Ha J, Ma Y, Grippin A, Jeong S, Antony A, Chang M, Kang M, Gallup T, Koong A, Li J, Yun K, Kim B, Jiang W. An antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy. Nature Cancer 2025, 6: 511-527. PMID: 40000910, DOI: 10.1038/s43018-025-00919-0.Peer-Reviewed Original ResearchConceptsAntibody-toxin conjugatesTumor cellsImmune recognition of tumor cellsEnhanced antigen cross-presentationRecognition of tumor cellsCancer cell phagocytosisTumor-derived antigensToxin listeriolysin OTumor-derived peptidesImproved animal survivalPromote immune recognitionCytosolic immune sensorsIntracellular bacterium Listeria monocytogenesTreatment in vivoTreating multiple cancersPhagocytosis checkpointsCheckpoint blockadeCancer immunotherapySignal CD47Listeriolysin OMetastatic breastMelanoma tumorsTherapeutic strategiesAnimal survivalCell phagocytosisDevelopment of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy
Bhatt D, Sundaram R, López K, Lee T, Gueble S, Vasquez J. Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. Current Protocols 2025, 5: e70097. PMID: 39995104, DOI: 10.1002/cpz1.70097.Peer-Reviewed Original ResearchConceptsImproved response to immune checkpoint blockadeGlioma modelResponse to immune checkpoint blockadeAlkylating agentsImmune checkpoint blockadeIncrease tumor immunogenicityMurine glioma modelMurine glioma cell lineResponse to alkylating agentsResistance to temozolomideDNA repair genotypesMMR deficiencyAntitumor immunityCheckpoint blockadeTumor immunogenicityMedian survivalImmunocompetent modelDismal prognosisMismatch repairMismatch repair deficiencyGlioma cell linesIntracranial tumorsAlkylating chemotherapySomatic lossSomatic acquisitionA Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types
Bex A, Jewett M, Lewis B, Abel E, Albiges L, Berg S, Bratslavsky G, Braun D, Brugarolas J, Choueiri T, Finelli A, George D, Haas N, Hakimi A, Hammers H, Hirsch M, Jonasch E, Kapur P, Linehan W, Master V, McGregor B, McKay R, Mehra R, Pal S, Poteat S, Powles T, Rossi S, Shapiro D, Signoretti S, Singer E, Stravin C, Tannir N, Vaishampayan U, Xu W, Stewart G. A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types. European Urology 2025, 87: 385-389. PMID: 39855942, DOI: 10.1016/j.eururo.2025.01.007.Peer-Reviewed Original ResearchBiological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach
Lopez de Rodas M, Villalba-Esparza M, Sanmamed M, Chen L, Rimm D, Schalper K. Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach. Nature Reviews Clinical Oncology 2025, 22: 163-181. PMID: 39820025, DOI: 10.1038/s41571-024-00984-x.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesImmune-checkpoint inhibitorsTumor-infiltrating lymphocyte subpopulationsClinical significance of tumor-infiltrating lymphocytesPredictive value of tumor-infiltrating lymphocytesSignificance of tumor-infiltrating lymphocytesStudy of tumor-infiltrating lymphocytesImmune-checkpoint inhibitor therapyImmune-mediated tumor eliminationEra of immunotherapyT cell dysfunctionBiomarkers of responseSolid tumor typesImmunotherapeutic approachesAntigen-reactiveTumor microenvironmentTumor typesClinical outcomesTumor eliminationClinical significanceSingle-cell transcriptomicsPredictive valueAnticancer mechanismClinical implicationsResistance mechanismsImmunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma
Jammihal T, Saliby R, Labaki C, Soulati H, Gallegos J, Peris A, McCurry D, Yu C, Shah V, Poduval D, El Zarif T, El Ahmar N, Laimon Y, Eid M, Sheshdeh A, Krajewski K, Büttner F, Schwab M, Heng D, Casellas R, Rai K, Zacharias Millward N, Msaouel P, Karam J, Signoretti S, Van Allen E, Choueiri T, Braun D, Shukla S. Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma. Nature Cancer 2025, 6: 372-384. PMID: 39789182, PMCID: PMC12121501, DOI: 10.1038/s43018-024-00896-w.Peer-Reviewed Original ResearchConceptsTertiary lymphoid structuresVascular endothelial growth factorRenal cell carcinomaCell carcinomaCytotoxic T-lymphocyte-associated protein 4 inhibitorsResponse to immune checkpoint inhibitionExceptional responseMetastatic clear cell renal cell carcinomaStandard-of-care immunotherapiesTertiary lymphoid structure formationCytotoxic T cell responsesClear cell renal cell carcinomaIO-based treatmentsTreatment-naive personsImmune checkpoint inhibitionImmune checkpoint inhibitorsCell renal cell carcinomaT cell responsesT-cell-directedEndothelial growth factorCell death proteinAntitumor immunityCheckpoint inhibitionCheckpoint inhibitorsNeoantigen loadBile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi S, Chen D, Liu Y, Johnson M, Miller C, Ganguly S, Lande K, LaPorta M, Hoffmann F, Mann T, Teneche M, Casillas E, Mangalhara K, Mathew V, Sun M, Jensen I, Farsakoglu Y, Chen T, Parisi B, Deota S, Havas A, Lee J, Chung H, Schietinger A, Panda S, Williams A, Farber D, Dhar D, Adams P, Feng G, Shadel G, Sundrud M, Kaech S. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science 2025, 387: 192-201. PMID: 39787217, DOI: 10.1126/science.adl4100.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsBile Acids and SaltsCarcinoma, HepatocellularCD8-Positive T-LymphocytesCell Line, TumorEndoplasmic Reticulum StressHepatocytesHumansImmune Checkpoint InhibitorsImmunotherapyLithocholic AcidLiver NeoplasmsMiceOxidative StressProgrammed Cell Death 1 ReceptorTumor MicroenvironmentUrsodeoxycholic AcidConceptsTumor-specific T-cell responsesT cell responsesAnti-programmed cell death protein 1Ursodeoxycholic acidCell death protein 1CD8<sup>+</sup> T cellsBile acidsFeatures of human hepatocellular carcinomaImprove tumor immunotherapyInfluence antitumor immunityT cell functionReduced tumor growthBA synthesisLiver cancer modelCancer model systemsHuman hepatocellular carcinomaLandscape of cancerAntitumor immunityTumor immunotherapySecondary bile acidsOrgan-specific metabolitesEndoplasmic reticulum stressT cellsCancer modelsDietary intakeSociety for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing
Taube J, Sunshine J, Angelo M, Akturk G, Eminizer M, Engle L, Ferreira C, Gnjatic S, Green B, Greenbaum S, Greenwald N, Hedvat C, Hollmann T, Jiménez-Sánchez D, Korski K, Lako A, Parra E, Rebelatto M, Rimm D, Rodig S, Rodriguez-Canales J, Roskes J, Schalper K, Schenck E, Steele K, Surace M, Szalay A, Tetzlaff M, Wistuba I, Yearley J, Bifulco C. Society for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing. Journal For ImmunoTherapy Of Cancer 2025, 13: e008875. PMID: 39779210, PMCID: PMC11749220, DOI: 10.1136/jitc-2024-008875.Peer-Reviewed Original ResearchMeSH KeywordsFluorescent Antibody TechniqueHumansImage Processing, Computer-AssistedImmunohistochemistryImmunotherapyNeoplasmsConceptsSociety for ImmunotherapyMultiplex immunohistochemistrySociety for Immunotherapy of CancerImmunotherapy of cancerImmune cell subsetsPractice guidelinesCell subsetsTumor microenvironmentGeneration of robust dataTask ForceComplex immunophenotypeAcademic centersMarker expressionMIHC/IFClinical useClinical implementationImmunohistochemistryQuantitative image analysisImmunofluorescenceDiagnostic companiesRobust dataAssayImage analysisManagement considerationsStaining protocolAutogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial
Lopez J, Powles T, Braiteh F, Siu L, LoRusso P, Friedman C, Balmanoukian A, Gordon M, Yachnin J, Rottey S, Karydis I, Fisher G, Schmidt M, Schuler M, Sullivan R, Burris H, Galvao V, Henick B, Dirix L, Jaeger D, Ott P, Wong K, Jerusalem G, Schiza A, Fong L, Steeghs N, Leidner R, Rittmeyer A, Laurie S, Gort E, Aljumaily R, Melero I, Sabado R, Rhee I, Mancuso M, Muller L, Fine G, Yadav M, Kim L, Leveque V, Robert A, Darwish M, Qi T, Zhu J, Zhang J, Twomey P, Rao G, Low D, Petry C, Lo A, Schartner J, Delamarre L, Mellman I, Löwer M, Müller F, Derhovanessian E, Cortini A, Manning L, Maurus D, Brachtendorf S, Lörks V, Omokoko T, Godehardt E, Becker D, Hawner C, Wallrapp C, Albrecht C, Kröner C, Tadmor A, Diekmann J, Vormehr M, Jork A, Paruzynski A, Lang M, Blake J, Hennig O, Kuhn A, Sahin U, Türeci Ö, Camidge D. Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. Nature Medicine 2025, 31: 152-164. PMID: 39762422, PMCID: PMC11750724, DOI: 10.1038/s41591-024-03334-7.Peer-Reviewed Original ResearchConceptsCD8+ T cellsAdvanced solid tumorsT cellsSolid tumorsCirculating CD8+ T cellsEfficacy of cancer immunotherapyTumor-infiltrating T cellsStimulate T cell responsesResponse to immunotherapyT cell responsesPreliminary antitumor activityPhase 1 studyPhase 1 trialDose escalationPretreated patientsCancer immunotherapyEvaluation of pharmacokineticsCD4+Tumor lesionsTreatment initiationTumor tissuesAtezolizumabClinical activityDisease characteristicsImmunotherapyLethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression
Jin K, Ding Y, Xu J, Liu Z, Zeng H, Su X, Zhang L, Sun J, Wu Y, Liu H, Chang Y, Zhu Y, Wang Z, Xu L, Zhang W, Xu J. Lethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression. Journal For ImmunoTherapy Of Cancer 2025, 13: e010964. PMID: 39762080, PMCID: PMC11749520, DOI: 10.1136/jitc-2024-010964.Peer-Reviewed Original ResearchConceptsMDM2</i> amplificationMurine double minute 2Programmed death-ligand 1Programmed death-1Platinum-based chemotherapyUrothelial carcinomaDedifferentiated morphologyClinical outcomesAbundance of CD8<sup>+</sup> T cellsCytotoxic T-lymphocyte-associated protein 4Anti-PD-1/PD-L1 immunotherapyAssociated with inferior overall survivalResponse to platinum-based chemotherapyExpression of immune checkpoint moleculesCD8<sup>+</sup> T cellsMurine double minute 2 amplificationDeath-ligand 1Immune checkpoint moleculesInferior overall survivalTumor immune contextureUbiquitin ligase murine double minute 2Subsets of patientsLethal clinical outcomeIndependent external cohortDouble minute 2
2024
A novel pharmacological entity toward integrated multimodal immunotherapy
Sirera R, Beltrán-Visiedo M, Galluzzi L. A novel pharmacological entity toward integrated multimodal immunotherapy. Trends In Pharmacological Sciences 2024, 46: 95-97. PMID: 39721827, DOI: 10.1016/j.tips.2024.12.001.Peer-Reviewed Original ResearchTertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities
Ruddle N. Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities. Methods In Molecular Biology 2024, 2864: 299-312. PMID: 39527229, DOI: 10.1007/978-1-0716-4184-2_16.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansImmune Checkpoint InhibitorsImmunotherapyNeoplasmsTertiary Lymphoid StructuresTumor MicroenvironmentConceptsImmune-related adverse eventsImmune checkpoint inhibitorsTertiary lymphoid structuresSecondary lymphoid organsTA-TLSSusceptibility to immune-related adverse eventsAssociated with favorable clinical outcomesPositive response to immunotherapyResponse to immunotherapyFavorable clinical outcomesCellular compositionVascular growth factorsAccumulation of lymphoid cellsCheckpoint inhibitorsLymphoid neogenesisLymphoid structuresProcess of lymphoid neogenesisClinical outcomesAdenovirus vectorLymphoid cellsTumor-associatedAdverse eventsTumor environmentOrgan rejectionChronic inflammationInterventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma.
Bitar R, Salem R, Finn R, Greten T, Goldberg S, Chapiro J. Interventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma. Radiology 2024, 313: e232875. PMID: 39560477, PMCID: PMC11605110, DOI: 10.1148/radiol.232875.Peer-Reviewed Original ResearchConceptsManagement of hepatocellular carcinomaHepatocellular carcinomaLocoregional therapyClinical trialsImage-guided locoregional therapiesEnd pointsStages of hepatocellular carcinomaTumor microenvironment mechanismsCatheter-directed therapyCombination of immunotherapyProspective clinical trialImaging end pointsStandard of careAdjuvant settingNovel immunotherapiesCombination therapyTherapy resistanceInterventional radiologistsImmunotherapyDisease stageTherapyDisease evolutionNovel biomarkersCarcinomaMicroenvironment mechanismsTofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study
Liu Q, Liu M, Zou Z, Lin J, Zhang N, Zhao L, Zhou J, Zhou H, Zhou X, Jiao X, Yu Y, Liu T. Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study. Journal Of Translational Medicine 2024, 22: 803. PMID: 39210332, PMCID: PMC11360683, DOI: 10.1186/s12967-024-05617-6.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsImmune checkpoint inhibitorsManagement of immune-related adverse eventsOverall survivalTofacitinib treatmentAdverse eventsTreatment of immune-related adverse eventsCancer patientsImmune checkpoint inhibitor initiationImmune checkpoint inhibitor myocarditisSteroid-resistant casesTreated with tofacitinibClinical remission rateResultsFifty-three patientsSafety of tofacitinibCardiac troponin TLife-threatening casesMulti-center observational studyAnti-tumor activityMultiple autoimmune diseasesBackgroundTreatment strategiesCheckpoint inhibitorsMedian OSSteroid taperCancer immunotherapyNovel immunotherapeutics against LGR5 to target multiple cancer types
Chen H, Mueller N, Stott K, Kapeni C, Rivers E, Sauer C, Beke F, Walsh S, Ashman N, O’Brien L, Rafati Fard A, Ghodsinia A, Li C, Joud F, Giger O, Zlobec I, Olan I, Aitken S, Hoare M, Mair R, Serrao E, Brenton J, Garcia-Gimenez A, Richardson S, Huntly B, Spring D, Skjoedt M, Skjødt K, de la Roche M, de la Roche M. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine 2024, 16: 2233-2261. PMID: 39169164, PMCID: PMC11393416, DOI: 10.1038/s44321-024-00121-2.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaColorectal cancerTarget multiple cancer typesBispecific T-cell engagerCell killing in vitroChimeric antigen receptorT-cell engagersCancer cells in vitroPre-B-ALLAnti-tumor efficacyCancer cell killing in vitroKilling in vitroCells in vitroAntibody-drug conjugatesMultiple cancer typesLgr5 overexpressionTumor burdenAntigen receptorMurine modelNovel immunotherapeuticsCancer modelsTumor cellsEffective modalityEffective tumorLgr5Immunotherapy For US Patients With Metastatic Cancer at the End of Life—Reply
Kerekes D, Khan S. Immunotherapy For US Patients With Metastatic Cancer at the End of Life—Reply. JAMA Oncology 2024, 10: 1134-1134. PMID: 38842840, DOI: 10.1001/jamaoncol.2024.1566.Peer-Reviewed Original ResearchBiomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee
Monette A, Warren S, Barrett J, Garnett-Benson C, Schalper K, Taube J, Topp B, Snyder A. Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee. Journal For ImmunoTherapy Of Cancer 2024, 12: e009427. PMID: 39032943, PMCID: PMC11261685, DOI: 10.1136/jitc-2024-009427.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorConsensusHumansImmune Checkpoint InhibitorsImmunotherapyNeoplasmsConceptsProgrammed cell death protein 1/programmed death-ligand 1PD-(L)1Biomarker developmentApplication of novel biomarkersPD-(L)1 therapyDeath-ligand 1Patient selection strategiesCombination therapyTumor typesTreatment optionsImmune biologyAxis inhibitionEffective treatmentCancer progressionNovel biomarkersPatientsTherapyImmunotherapyBiomarkersKnowledge of mechanismsDelivery of effective treatmentTreatmentAgentsTumorProgression
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