2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchMeSH KeywordsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansLung NeoplasmsSignal TransductionConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations
2015
Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
2013
Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors
Jimeno A, Weiss GJ, Miller WH, Gettinger S, Eigl BJ, Chang AL, Dunbar J, Devens S, Faia K, Skliris G, Kutok J, Lewis KD, Tibes R, Sharfman WH, Ross RW, Rudin CM. Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors. Clinical Cancer Research 2013, 19: 2766-2774. PMID: 23575478, PMCID: PMC3694426, DOI: 10.1158/1078-0432.ccr-12-3654.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlanine TransaminaseAlopeciaArea Under CurveAspartate AminotransferasesDose-Response Relationship, DrugDrug Administration ScheduleFatigueFemaleFollow-Up StudiesHedgehog ProteinsHumansMaleMetabolic Clearance RateMiddle AgedNauseaNeoplasmsSignal TransductionSpasmTreatment OutcomeVeratrum AlkaloidsConceptsBasal cell carcinomaDose-limiting toxicityInhibitor-naïve patientsIPI-926Alanine aminotransferaseSolid tumorsAspartate aminotransferaseAccelerated titration scheduleDose-escalation cohortsPhase II doseResponse Evaluation CriteriaSingle-agent activityHuman phase ISolid Tumors assessmentHematologic toxicityStarting doseAdult patientsStandard therapyMuscle spasmTitration scheduleReversible elevationCell carcinomaQD dosingTumor assessmentPharmacokinetic profile
2010
Management of Patients with Advanced Non-Small Cell Lung Cancer
Triano LR, Deshpande H, Gettinger SN. Management of Patients with Advanced Non-Small Cell Lung Cancer. Drugs 2010, 70: 167-179. PMID: 20108990, DOI: 10.2165/11532200-000000000-00000.Peer-Reviewed Original ResearchConceptsAdvanced non-small cell lung cancerNon-small cell lung cancerCell lung cancerEpidermal growth factor receptorGrowth factor receptorOverall survivalLung cancerThird-line treatmentFirst-line chemotherapyFactor receptorManagement of patientsVascular endothelial growth factorQuality of lifeEndothelial growth factorMedian survivalSystemic therapyRandomized trialsTraditional chemotherapySmall molecule inhibitorsFDA approvalUS FDAChemotherapyKey mediatorGrowth factorAdditional agents
2008
Targeted Therapy in Advanced Non-Small-Cell Lung Cancer
Gettinger S. Targeted Therapy in Advanced Non-Small-Cell Lung Cancer. Seminars In Respiratory And Critical Care Medicine 2008, 29: 291-301. PMID: 18506667, DOI: 10.1055/s-2008-1076749.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBenzenesulfonatesBevacizumabCarcinoma, Non-Small-Cell LungDrug Delivery SystemsEpidermal Growth FactorErlotinib HydrochlorideHumansIndolesLung NeoplasmsNiacinamidePhenylurea CompoundsPiperidinesProtein Kinase InhibitorsPyridinesPyrrolesQuinazolinesSignal TransductionSorafenibSunitinibTreatment OutcomeVascular Endothelial Growth Factor AConceptsPhase II trialLung cancerEpidermal growth factor receptorII trialEGFR inhibitorsSmall molecule inhibitorsAdvanced non-small cell lung cancerNon-small cell lung cancerStandard first-line chemotherapyVascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayCancer cell pathwaysStandard salvage chemotherapyFirst-line chemotherapyPhase III studyPhase III trialsCell lung cancerSignificant survival advantageEGFR gene mutationsLeast equivalent activityVEGF receptor tyrosine kinasesCancer cell proliferationGrowth factor pathwaysGrowth factor receptorSalvage chemotherapy