2017
CDK4/6 inhibition triggers anti-tumour immunity
Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, Hoog J, Ellis MJ, Ma CX, Ramm S, Krop IE, Winer EP, Roberts TM, Kim HJ, McAllister SS, Zhao JJ. CDK4/6 inhibition triggers anti-tumour immunity. Nature 2017, 548: 471-475. PMID: 28813415, PMCID: PMC5570667, DOI: 10.1038/nature23465.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationBiological MimicryBreast NeoplasmsCell Cycle CheckpointsCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalFemaleHumansInterferonsMicePhosphorylationProtein Kinase InhibitorsRepressor ProteinsRNA, Double-StrandedSignal TransductionT-Lymphocytes, RegulatoryTranscriptomeViruses
2016
Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors
Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. Cancer Cell 2016, 29: 255-269. PMID: 26977878, PMCID: PMC4794996, DOI: 10.1016/j.ccell.2016.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalDrug Resistance, NeoplasmErbB ReceptorsFemaleHumansMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesNeoplasm Recurrence, LocalPhosphorylationProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsHER2-positive breast cancerCDK4/6 inhibitorsBreast cancerEGFR/HER2Patient-derived xenograft tumorsTransgenic mouse modelInhibition of CDK4/6Tumor recurrenceXenograft tumorsMouse modelPotent suppressionTransgenic modelClinical specimensTherapeutic resistanceDual inhibitionMediate resistanceHER2CancerTSC2 phosphorylationG1 arrestCellular senescenceTherapyRb phosphorylationTumorsCDK4/6Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer
Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Jin Huh S, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Peluffo G, Brown J, D’Santos C, Krop I, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao P, Duarte M, Wu S, Chiang C, Anders L, Young R, Winer E, Letai A, Barry W, Carroll J, Long H, Brown M, Shirley Liu X, Meyer C, Bradner J, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature 2016, 529: 413-417. PMID: 26735014, PMCID: PMC4854653, DOI: 10.1038/nature16508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzepinesBinding, CompetitiveCasein Kinase IICell Cycle ProteinsCell Line, TumorCell ProliferationChromatinDrug Resistance, NeoplasmEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGenome, HumanHumansMediator Complex Subunit 1MiceNuclear ProteinsPhosphorylationPhosphoserineProtein BindingProtein Phosphatase 2Protein Structure, TertiaryProteomicsTranscription FactorsTranscription, GeneticTriazolesTriple Negative Breast NeoplasmsXenograft Model Antitumor Assays
2015
PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers
Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene 2015, 35: 3607-3612. PMID: 26500061, PMCID: PMC4846581, DOI: 10.1038/onc.2015.406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmFemaleHumansLapatinibMammary Neoplasms, ExperimentalMice, KnockoutMolecular Targeted TherapyPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseQuinazolinesReceptor, ErbB-2Signal TransductionThiazolesTumor BurdenXenograft Model Antitumor AssaysConceptsBreast tumorsP110β inhibitorsHuman epidermal growth factor receptor 2 (HER2) amplificationP110α inhibitionPTEN lossInhibition of HER2Treatment of HER2Human cancersPI3K pathway activationPTEN-deficient breast cancersGenetic mouse modelsPI3K/Akt signalingPTEN-deficient tumorsPI3K/AktDual HER2Therapeutic regimenHER2 inhibitionPIK3CA mutationsTumor regressionBreast cancerMouse modelXenograft modelHER2Null tumorsHER2 activation
2013
Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry
Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, Dorfman D, Pinkus G, Weigert O, Hornick JL, Chirieac LR, Hirsch M, Oh DJ, South AP, Leigh IM, Pourreyron C, Cassidy AJ, DeAngelo DJ, Weinstock DM, Krop IE, Dillon D, Brock JE, Lazar AJ, Peto M, Cho RJ, Stoeck A, Haines BB, Sathayanrayanan S, Rodig S, Aster JC. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry. PLOS ONE 2013, 8: e67306. PMID: 23825651, PMCID: PMC3688991, DOI: 10.1371/journal.pone.0067306.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorHeterograftsHumansImmunohistochemistryMiceMutationReceptor, Notch1ConceptsCell lymphomaNotch1 activationNOTCH1 mutationsPeripheral T-cell lymphomaNon-small cell lung carcinomaLymphoblastic leukemia/lymphomaTriple-negative breast cancerLarge B-cell lymphomaSelection of patientsChronic lymphocytic leukemia cellsT-cell lymphomaCell lung carcinomaNegative breast cancerChronic lymphocytic leukemiaLeukemia/lymphomaB-cell lymphomaMantle cell lymphomaB-cell tumorsRole of Notch1Lymphocytic leukemia cellsLymph nodesAngioimmunoblastic lymphomaCell tumorsClinical trialsOvarian carcinoma
2011
Ribavirin Treatment Effects on Breast Cancers Overexpressing eIF4E, a Biomarker with Prognostic Specificity for Luminal B-Type Breast Cancer
Pettersson F, Yau C, Dobocan MC, Culjkovic-Kraljacic B, Retrouvay H, Puckett R, Flores LM, Krop IE, Rousseau C, Cocolakis E, Borden KL, Benz CC, Miller WH. Ribavirin Treatment Effects on Breast Cancers Overexpressing eIF4E, a Biomarker with Prognostic Specificity for Luminal B-Type Breast Cancer. Clinical Cancer Research 2011, 17: 2874-2884. PMID: 21415224, PMCID: PMC3086959, DOI: 10.1158/1078-0432.ccr-10-2334.Peer-Reviewed Original ResearchMeSH KeywordsAntimetabolites, AntineoplasticBiomarkers, TumorBreast NeoplasmsCarcinomaCell Line, TumorCells, CulturedEukaryotic Initiation Factor-4EFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansMammary Glands, HumanOrgan SpecificityPrognosisRibavirinRNA, Small InterferingUp-RegulationConceptsDistant metastasis-free survivalBreast cancer cell linesBreast cancerCancer cell linesLuminal B type breast cancerNode-negative breast cancerIntrinsic breast cancer subtypesPoor outcome groupMetastasis-free survivalLuminal B casesSpecific molecular subtypesCell proliferationBreast cancer subtypesCell linesBreast cancer cellsSpecific molecular profilePrognostic specificityMetastatic diseasePrognostic valuePrimary tumorCancer therapeutic strategiesOutcome groupSkin biopsiesMolecular subtypesPatient tumorsGPHMM: an integrated hidden Markov model for identification of copy number alteration and loss of heterozygosity in complex tumor samples using whole genome SNP arrays
Li A, Liu Z, Lezon-Geyda K, Sarkar S, Lannin D, Schulz V, Krop I, Winer E, Harris L, Tuck D. GPHMM: an integrated hidden Markov model for identification of copy number alteration and loss of heterozygosity in complex tumor samples using whole genome SNP arrays. Nucleic Acids Research 2011, 39: 4928-4941. PMID: 21398628, PMCID: PMC3130254, DOI: 10.1093/nar/gkr014.Peer-Reviewed Original Research
2010
Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists
Yang XH, Flores LM, Li Q, Zhou P, Xu F, Krop IE, Hemler ME. Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists. Cancer Research 2010, 70: 2256-2263. PMID: 20197472, PMCID: PMC3310185, DOI: 10.1158/0008-5472.can-09-4032.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntigens, CDAntineoplastic AgentsBreast NeoplasmsCell Adhesion MoleculesCell Line, TumorDrug SynergismEnzyme ActivationFocal Adhesion Protein-Tyrosine KinasesHumansIntegrin alpha3beta1Integrin alpha6beta4LapatinibProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2Signal TransductionTetraspanin 24TrastuzumabConceptsAnti-ErbB2 agentsBreast cancer cellsHuman ErbB2Cancer cellsSensitizes breast cancer cellsTetraspanin protein CD151Mammary tumor cellsFocal adhesion kinaseLaminin-5ErbB2 antagonistTrastuzumab treatmentBreast cancerLaminin-binding integrinsDrug resistanceTumor cellsCD151 knockdownLaminin-integrinErbB2TrastuzumabCancerCD151CellsTreatmentKnockdownAgents
2005
HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation
Krop I, Parker MT, Bloushtain-Qimron N, Porter D, Gelman R, Sasaki H, Maurer M, Terry MB, Parsons R, Polyak K. HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation. Cancer Research 2005, 65: 9659-9669. PMID: 16266985, DOI: 10.1158/0008-5472.can-05-1663.Peer-Reviewed Original ResearchConceptsTumor suppressor functionHIN-1Suppressor functionMitogen-induced phosphorylationCell growthPotential tumor suppressor functionAnchorage-independent cell growthCell cycle reentryActivation of AktCell cycle arrestActivates AktRetinoblastoma proteinHIN-1 geneGrowth arrestAkt activationRb phosphorylationApparent cell cycle arrestLigand-binding studiesCell migrationCycle arrestPhosphorylationAktEpithelial cellsProteinPotent inhibitor
2004
Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types.
Krop I, Player A, Tablante A, Taylor-Parker M, Lahti-Domenici J, Fukuoka J, Batra SK, Papadopoulos N, Richards WG, Sugarbaker DJ, Wright RL, Shim J, Stamey TA, Sellers WR, Loda M, Meyerson M, Hruban R, Jen J, Polyak K. Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Molecular Cancer Research 2004, 2: 489-94. PMID: 15383627, DOI: 10.1158/1541-7786.489.2.9.Peer-Reviewed Original ResearchConceptsHIN-1 expressionHIN-1 methylationHIN-1Breast carcinomaPancreatic carcinomaSmall cell lung cancerNormal tissuesMajority of lungCell lung cancerSquamous cell carcinomaMultiple human cancer typesPromoter methylationMultiple human tumor typesBronchial epithelial cellsHuman cancer typesHuman tumor typesNoncancer patientsCell carcinomaPromoter methylation statusLung cancerBronchial lavagePremalignant changesLack of expressionLung carcinomaProstate tumors