grant
Dual targeting of PI3K and NOS pathways in Metaplastic BreastCancer (MBC)
Organization METHODIST HOSPITAL RESEARCH INSTITUTELocation HOUSTON, UNITED STATESPosted 8 Jul 2023Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY20253-Phosphoinositide Dependent Protein Kinase-1AKTAccountingAcetatesAdhesionsAfter CareAfter-TreatmentAftercareAkt proteinAntioncogene Protein p53ApoptosisApoptosis PathwayArginineBiopsyBreast CancerBreast Cancer ModelBreast Cancer PatientBreast Cancer cell lineBreast PDX modelsBreast Tumor PatientBreast tumor cell lineBreast tumor modelCancersCatalytic CoreCatalytic DomainCatalytic RegionCatalytic SiteCatalytic SubunitCell BodyCell CommunicationCell InteractionCell LineCell LocomotionCell MigrationCell MovementCell to Cell Communication and SignalingCell-Cell SignalingCell-to-Cell InteractionCellLineCellsCellular ExpansionCellular GrowthCellular MigrationCellular MotilityCellular Tumor Antigen P53ChemoresistanceClinical TrialsCombined Modality TherapyComplementComplement ProteinsCytotoxic agentCytotoxic drugD-NMMADNA mutationDataData AnalysesData AnalysisDetectionDevelopmentDiseaseDisorderDrug resistanceDrugsEDRF SynthaseEndocrine TherapyEndogenous Nitrate VasodilatorEndothelium-Derived Growth Factor SynthaseEndothelium-Derived Nitric OxideEnvironmentEventExhibitsFundingGeneral Prognostic FactorGeneralized GrowthGenesGenetic ChangeGenetic defectGenetic mutationGrowthGuanylyl Cyclase-Activating Factor SynthaseHealthHormonal TherapyINOSImageImmunocompetentImmunofluorescenceImmunofluorescence ImmunologicInducible Nitric Oxide SynthaseInositide PhospholipidsInositol PhosphoglyceridesInositol PhospholipidsInvadedInvestigationIsoformsKinasesL-ArginineL-MonomethylarginineL-NMMALymphoid CellMMAC1MMAC1 proteinMacrophageMacrophage Nitric Oxide SynthaseMalignant Breast NeoplasmMalignant NeoplasmsMalignant TumorMediatingMedicationMetaplastic breast cancerMetaplastic carcinoma of the breastMetastasisMetastasis to the LungMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to the LungMetastatic TumorMetastatic Tumor to the LungMiceMice MammalsModelingMolecularMononitrogen MonoxideMultimodal TherapyMultimodal TreatmentMurineMusMutateMutated in Multiple Advanced Cancers 1MutationMyeloid CellsMφN(G)-MethylarginineN(G)-Monomethyl-D-ArginineN(G)-MonomethylarginineN(omega)-Monomethyl-L-ArginineN-MethylarginineNG-Monomethyl-L-ArginineNO SynthaseNOS2NOS2ANOS2A geneNOS2A, Inducible, HepatocyteNeoplasm MetastasisNitric OxideNitric Oxide SynthaseNitric Oxide Synthase 2ANitric Oxide Synthetase InhibitorNitric-Oxide SynthetaseNitrogen MonoxideNitrogen ProtoxideNon-Polyadenylated RNAOncogenesisOncogenicOncoprotein p53P53PDX modelPHTS genePHTS proteinPI3K-AlphaPIK3-AlphaPIK3CAPIK3CA genePIQRAYPKB KinasePTENPTEN genePTEN proteinPTEN1Pathway interactionsPatient derived xenograftPatient-derived xenograft models of breast cancerPatientsPharmaceutical PreparationsPhosphatase and Tensin HomologPhosphatase and Tensin Homolog Deleted on Chromosome 10Phosphatidyl InositolPhosphatidylinositol 3-Kinase, Catalytic, 110-kD, AlphaPhosphatidylinositol 3-Kinase, Catalytic, AlphaPhosphatidylinositolsPhosphoinositidesPhosphoprotein P53Phosphoprotein pp53Phosphotransferase GenePhosphotransferasesPopulationPre-Clinical ModelPreclinical ModelsPrimary NeoplasmPrimary TumorProductionPrognosisPrognostic FactorPrognostic/Survival FactorProgrammed Cell DeathPropertyProtein IsoformsProtein Kinase BProtein TP53Proto-Oncogene Proteins c-aktPtdInsPublishingRAC-PK proteinRNARNA Gene ProductsRNA SeqRNA and protein interactionRNA sequencingRNA-Protein InteractionRNAseqRadiation therapyRadiotherapeuticsRadiotherapyRefractoryRegimenResearch SpecimenResistanceResolutionRibo-seqRibonucleic AcidRibosomal ProteinsRibosomesRoleSUM-159SUM-159 Breast Cancer Cell LineSUM159Secondary NeoplasmSecondary TumorSignal PathwaySpecimenStrains Cell LinesStromal CellsSurvey InstrumentSurveysSurvival RateTNBCTP53TP53 geneTRP53TestingTherapeuticTissue GrowthTranslationsTransphosphorylasesTreatment EfficacyTumor CellTumor Protein p53Tumor Protein p53 Genealpelisibbreast cancer PDXbreast cancer patient-derived xenograftc-akt proteincancer metastasiscancer microenvironmentcancer sub-typescancer subtypescell growthcell motilitycell typechemoresistantchemotherapychemotherapy resistancechemotherapy resistantclinical prognosiscombination therapycombinatorialcombined modality treatmentcombined treatmentcomplementationcultured cell linedata interpretationdetermine efficacydevelopmentaldrug resistantdrug/agentdruggable targetefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationendothelial cell derived relaxing factorevaluate efficacyexamine efficacygain of functiongenome mutationhPDK1hormone therapyimagingimaging systemimmune competentin vivoindividuals with breast cancerinhibitorintercellular communicationintervention efficacylung metastasismalignancymalignant breast tumormammary cancer modelmammary tumor modelmetastasize to the lungmouse modelmulti-modal datamulti-modal datasetsmulti-modal therapymulti-modal treatmentmultimodal datamultimodal datasetsmurine modelmutated in multiple advanced cancers 1 proteinneoplasm/cancerneoplastic cellnitric oxide synthase inhibitoromega-N-Methylarginineontogenyoutcome predictionp110-Alphap53 Antigenp53 Genesp53 Tumor Suppressorparticipant enrollmentpathwaypatient derived xenograft modelpatient enrollmentpatients with breast cancerperson with breast cancerphosphatase and tensin homologue on chromosome tenpost treatmentpre-clinicalpreclinicalprogenitor cell regenerationprogenitor cell self renewalprogenitor regenerationprogenitor self renewalprotein kinase B kinaseprotein p53proto-oncogene protein RACproto-oncogene protein aktpulmonary metastasisrac protein kinaseradiation treatmentrelated to A and C-proteinresistance to Drugresistance to therapyresistantresistant to Drugresistant to therapyresolutionsresponseresponse to therapyresponse to treatmentribosome footprint profilingribosome profilingsocial rolespatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicsstem and progenitor cell regenerationstem and progenitor cell self renewalstem cell regenerationstem cell self renewaltaxanetherapeutic efficacytherapeutic resistancetherapeutic responsetherapeutically effectivetherapy efficacytherapy resistanttherapy responsetranscriptome sequencingtranscriptomic sequencingtranslationtreatment resistancetreatment responsetreatment responsivenesstreatment with radiationtriple-negative breast cancertriple-negative invasive breast carcinomatumortumor cell metastasistumor growthtumor microenvironmenttumorigenesis
Description preview
ABSTRACT
Metaplastic breast cancer (MpBC) is a rare subset accounting for <5% of all breast cancers. MpBC is a significant
health challenge as it exhibits the most dismal prognosis of all breast cancer subtypes, worse than non-MpBC
triple-negative breast cancer (TNBC), with median survival rate of 8 months or less in patients with metastatic…
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