2020
PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expressionAcquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2019
Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.Peer-Reviewed Original ResearchConceptsNormalization cancer immunotherapyTumor microenvironmentSiglec-15Antibody blockadeCancer immunotherapyImmune suppressorMyeloid cellsAntigen-specific T cell responsesB7-H1/PDTumor-infiltrating myeloid cellsB7-H1 moleculesAnti-tumor immunityT cell responsesPotential targetImmune evasion mechanismsInhibits tumor growthMacrophage colony-stimulating factorColony-stimulating factorB7-H1Evasion mechanismsMouse modelHuman cancer cellsTumor growthCell responsesGenetic ablation
2018
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nature Communications 2018, 9: 3196. PMID: 30097571, PMCID: PMC6086912, DOI: 10.1038/s41467-018-05032-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BlockingCarcinogenesisCarcinoma, Non-Small-Cell LungCell ProliferationCytotoxicity, ImmunologicHistocompatibility Antigens Class IHumansLung NeoplasmsLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred NODMice, SCIDMutant ProteinsMutationPeptidesPhenotypeProgrammed Cell Death 1 ReceptorReproducibility of ResultsSurvival AnalysisTobaccoConceptsImmune checkpoint blockersCheckpoint blockersQuantitative immunofluorescenceNon-small cell lung carcinoma patientsCell lung carcinoma patientsNon-small cell lung carcinomaPatient-derived xenograft modelsIntratumoral T cellsMultiplexed quantitative immunofluorescencePD-1 blockadeLevels of CD3Lung carcinoma patientsCell lung carcinomaT cell proliferationPre-treatment samplesTIL phenotypeSurvival benefitCarcinoma patientsEffector capacityLung carcinomaT cellsWhole-exome DNA sequencingXenograft modelFavorable responseBlockers
2017
ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkers
2016
Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions
Gao B, Huang C, Kernstine K, Pelekanou V, Kluger Y, Jiang T, Peters-Hall JR, Coquelin M, Girard L, Zhang W, Huffman K, Oliver D, Kinose F, Haura E, Teer JK, Rix U, Le AT, Aisner DL, Varella-Garcia M, Doebele RC, Covington KR, Hampton OA, Doddapaneni HV, Jayaseelan JC, Hu J, Wheeler DA, Shay JW, Rimm DL, Gazdar A, Minna JD. Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions. Oncotarget 2016, 5: 11114-11126. PMID: 28052041, PMCID: PMC5355251, DOI: 10.18632/oncotarget.14366.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAdultAgedAged, 80 and overBase SequenceCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCells, CulturedCoculture TechniquesDNA Copy Number VariationsDNA Mutational AnalysisEpithelial CellsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationRespiratory MucosaTumor Cells, CulturedConceptsNon-small cell lung cancerRespiratory epithelial cellsNon-malignant lungCell lung cancerCRC culturesLung cancerEpithelial cellsResected non-small cell lung cancerPrimary lung cancerNon-malignant samplesLung epithelial cellsRho-kinase inhibitorNon-malignant cellsPrimary NSCLCPrimary tumorDiploid patternOriginal tumorTumor specimensTumor tissueTumorsKinase inhibitorsCancerCancer cellsMRNA expression profilesSmall subpopulationTriple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence
Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Dávila-González D, Wang K, Sánchez V, Dean PT, Combs SE, Hicks D, Pinto JA, Landis MD, Doimi FD, Yelensky R, Miller VA, Stephens PJ, Rimm DL, Gómez H, Chang JC, Sanders ME, Cook RS, Arteaga CL. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Science Translational Medicine 2016, 8: 334ra53. PMID: 27075627, PMCID: PMC5256931, DOI: 10.1126/scitranslmed.aad3001.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell Line, TumorCell ProliferationChromosomes, Human, Pair 9Cohort StudiesFemaleGene AmplificationGene Knockdown TechniquesGenetic LociHumansJanus Kinase 2Middle AgedSignal TransductionSpheroids, CellularSTAT3 Transcription FactorSTAT6 Transcription FactorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerJAK2 amplificationBreast cancerUntreated triple-negative breast cancerEventual metastatic spreadBasal-like cancersBreast cancer subtypesTNBC cell linesAmplification of JAK2Janus kinase 2 (JAK2) geneNeoadjuvant chemotherapyOverall survivalTNBC xenograftsJAK1/2 inhibitorClinical trialsMetastatic spreadKinase 2 geneJAK2-specific inhibitorTumor growthCancer subtypesMammosphere formationPatientsPotential biomarkersTumor progressionJAK2 inhibitors
2012
Lin28 regulates HER2 and promotes malignancy through multiple mechanisms
Feng C, Neumeister V, Ma W, Xu J, Lu L, Bordeaux J, Maihle NJ, Rimm DL, Huang Y. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle 2012, 11: 2486-2494. PMID: 22713243, DOI: 10.4161/cc.20893.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2HER2 expressionLin28 expressionEpidermal growth factor receptor 2Growth factor receptor 2Primary breast tumorsFactor receptor 2Cancer cell growthMajor therapeutic targetMultiple mechanismsAdvanced human malignanciesClinical outcomesPoor prognosisBreast cancerReceptor 2Therapeutic targetBreast tumorsNovel mechanistic insightsHuman malignanciesLin28 overexpressionReceptor tyrosine kinasesCancerCell proliferationHuman cancersPowerful predictorMulti-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cells
2011
Making Every Cell Like HeLa A Giant Step For Cell Culture
Agarwal S, Rimm DL. Making Every Cell Like HeLa A Giant Step For Cell Culture. American Journal Of Pathology 2011, 180: 443-445. PMID: 22192626, DOI: 10.1016/j.ajpath.2011.12.001.Peer-Reviewed Original ResearchTargeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer
Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M. Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell 2011, 20: 119-131. PMID: 21741601, PMCID: PMC3180861, DOI: 10.1016/j.ccr.2011.05.026.Peer-Reviewed Original ResearchMeSH KeywordsAndrogensAnilidesAnimalsBeta CateninBreast NeoplasmsCell Line, TumorCell ProliferationDihydrotestosteroneFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaHumansMiceNitrilesReceptor, ErbB-2Receptors, AndrogenReceptors, EstrogenSignal TransductionTosyl CompoundsTranscriptional ActivationUp-RegulationWnt ProteinsXenograft Model Antitumor AssaysConceptsAndrogen receptorBreast cancerEstrogen receptorER-/HER2Estrogen receptor-negative breast cancerReceptor-negative breast cancerBreast cancer growthER- breast tumorsPotential therapeutic approachTumor cell growthAndrogen-regulated gene expressionEndocrine therapyER statusTherapeutic approachesAR cistromeBreast tumorsCancer growthDirect transcriptional inductionCancerHER2Ligand-dependent activationReceptorsSpecific targetingTumorsCell growth
2009
C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Jilaveanu LB, Zito CR, Aziz SA, Conrad PJ, Schmitz JC, Sznol M, Camp RL, Rimm DL, Kluger HM. C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas. Clinical Cancer Research 2009, 15: 5704-5713. PMID: 19737955, PMCID: PMC2763114, DOI: 10.1158/1078-0432.ccr-09-0198.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBenzenesulfonatesCell Line, TumorCell ProliferationCell SurvivalCohort StudiesDisease ProgressionFemaleGene SilencingHumansIndolesMaleMelanomaMiddle AgedNevusNiacinamidePhenolsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafPyridinesRNA, Small InterferingSensitivity and SpecificitySkin NeoplasmsSorafenibYoung AdultConceptsExtracellular signal-regulated kinaseC-RafC-Raf expressionSubset of melanomasPhospho-c-RafSignal-regulated kinaseCell linesProtein kinase inhibitionMitogen-activated protein kinase inhibitionDecreased viabilityDecreased Bcl-2 expressionProtein kinaseCell signalingBcl-2 inhibitionRaf kinaseB-RafMelanoma cell linesPhospho-MEKSpecific siRNAsSitu protein expressionGW5074Major isoformsKinasePhospho-ERKBcl-2 expressionPhosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma
Aziz SA, Davies M, Pick E, Zito C, Jilaveanu L, Camp RL, Rimm DL, Kluger Y, Kluger HM. Phosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma. Clinical Cancer Research 2009, 15: 3029-3036. PMID: 19383818, PMCID: PMC4431617, DOI: 10.1158/1078-0432.ccr-08-2768.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCell ProliferationChromonesEnzyme InhibitorsHumansImmunoblottingImmunoenzyme TechniquesMelanomaMorpholinesNevus, PigmentedPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Array AnalysisSkin NeoplasmsTissue Array AnalysisTumor Cells, CulturedConceptsPhosphatidylinositol-3 kinasePI3K inhibitorsExpression of p85PI3KP110alpha subunitPathway membersK inhibitorsCell linesPI3K pathway membersReverse phase protein arrayGood drug targetPhase protein arrayPI3K pathwayTargets of drugsCellular processesPhospho-Akt levelsPI3K inhibitionMelanoma cell linesDrug targetsFull activationP85K pathwayLY294002Protein arraysResistant cell linesActivated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model
Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT. Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1193-1198. PMID: 19144919, PMCID: PMC2626610, DOI: 10.1073/pnas.0811902106.Peer-Reviewed Original ResearchConceptsBeta-catenin signalingNormal melanocyte developmentTranscriptional profiling revealsWnt/beta-catenin signalingMelanoma cellsUp-regulates genesWnt/ß-cateninMelanoma progressionSmall molecule activatorsRole of WntMelanocyte developmentCell fateTranscriptional changesB16 murine melanoma cellsCellular differentiationProfiling revealsMelanocyte differentiationMelanoma cell linesMurine melanoma cellsß-cateninHuman melanoma cell linesWnt3aMurine melanoma modelCell linesReduced expression