2022
Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clinical Cancer Research 2022, 29: 174-182. PMID: 36074155, PMCID: PMC9811155, DOI: 10.1158/1078-0432.ccr-22-1138.Peer-Reviewed Original ResearchConceptsBreast cancer brain metastasesActive brain metastasesObjective response rateCNS objective response rateCancer brain metastasesBrain metastasesT-DXdPatient-derived xenograftsPDX modelsCohort studyTrastuzumab deruxtecanClinical efficacyClinical trialsHER2-positive breast cancer brain metastasesMetastatic HER2-positive breast cancerResponse rateMulti-institutional cohort studyHER2-positive breast cancerRetrospective multi-institutional cohort studyOrthotopic patient-derived xenograftsRetrospective cohort studyProspective clinical trialsSubset of patientsCentral nervous system activityPivotal clinical trialsp16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Ni J, Kabraji S, Xie S, Wang Y, Pan P, He X, Liu Z, Leone JP, Long HW, Brown MA, Winer EP, Dillon DAR, Lin NU, Zhao JJ. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications 2022, 13: 1473. PMID: 35304445, PMCID: PMC8933392, DOI: 10.1038/s41467-022-29081-2.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsBrain metastasesMetastatic HER2-positive breast cancerBiomarker-driven clinical trialsBreast cancer brain metastasesHER2-positive breast cancerOrthotopic patient-derived xenograftsMajority of HER2Cancer brain metastasesCDK4/6 inhibitionProtein immunohistochemistryClinical trialsBreast cancerHER2Tumor suppressor p16INK4aPatientsMetastasisBCBMAbemaciclibTucatinibXenograftsImmunohistochemistryCancerCDK4/6Trials
2016
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMice