The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer
Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, Kim D, Luo F, Mao P, Helvie K, Kowalski KJ, Nayar U, Waks AG, Parsons SH, Martinez R, Litchfield LM, Ye XS, Yu C, Jansen VM, Stille JR, Smith PS, Oakley GJ, Chu QS, Batist G, Hughes ME, Kremer JD, Garraway LA, Winer EP, Tolaney SM, Lin NU, Buchanan SG, Wagle N. The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer. Cancer Discovery 2020, 10: 1174-1193. PMID: 32404308, PMCID: PMC8815415, DOI: 10.1158/2159-8290.cd-19-1390.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiopsyBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCheckpoint Kinase 1Drug Resistance, NeoplasmExome SequencingFemaleGenomicsHumansProtein Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Receptors, SteroidRetinoblastoma Binding ProteinsUbiquitin-Protein LigasesConceptsCyclin-dependent kinase 4/6 inhibitorsMetastatic breast cancerBreast cancerResistant tumorsHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerReceptor-positive breast cancerEstrogen receptor expressionCandidate resistance mechanismsWhole-exome sequencingPrecision-based approachesCDK4/6i resistanceMechanisms of resistanceReceptor expressionTherapeutic strategiesCDK4/6iTherapeutic opportunitiesPatient samplesTumorsIssue featurePatientsCancerAcquired ResistanceCancer cellsAlterationsReversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer
Waks AG, Cohen O, Kochupurakkal B, Kim D, Dunn CE, Buendia J, Wander S, Helvie K, Lloyd MR, Marini L, Hughes ME, Freeman SS, Ivy SP, Geradts J, Isakoff S, LoRusso P, Adalsteinsson VA, Tolaney SM, Matulonis U, Krop IE, D’Andrea A, Winer EP, Lin NU, Shapiro GI, Wagle N. Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer. Annals Of Oncology 2020, 31: 590-598. PMID: 32245699, PMCID: PMC7946408, DOI: 10.1016/j.annonc.2020.02.008.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPlatinum chemotherapyDNA-damaging therapyMechanisms of resistanceBreast cancerMetastatic breast cancer patientsBreast cancer patientsTumor DNA sequencingNovel sequence alterationsWhole-exome sequencingDNA-damaging therapiesTreatment failureCancer patientsFunctional statusDisease progressionTumor biopsiesClinical cohortImmunohistochemical stainingSubsequent linesBRCA1/2 mutationsTherapeutic benefitPatientsUseful biomarkerFunctional assessmentTumor sections