2023
AKT/mTOR signaling modulates resistance to endocrine therapy and CDK4/6 inhibition in metastatic breast cancers
Abu-Khalaf M, Alex Hodge K, Hatzis C, Baldelli E, El Gazzah E, Valdes F, Sikov W, Mita M, Denduluri N, Murphy R, Zelterman D, Liotta L, Dunetz B, Dunetz R, Petricoin E, Pierobon M. AKT/mTOR signaling modulates resistance to endocrine therapy and CDK4/6 inhibition in metastatic breast cancers. Npj Precision Oncology 2023, 7: 18. PMID: 36797347, PMCID: PMC9935518, DOI: 10.1038/s41698-023-00360-5.Peer-Reviewed Original ResearchEndocrine therapyProgressive diseaseCDK4/6 inhibitionImmune cellsTumor epitheliumOpen-label multicenter clinical trialMetastatic breast cancer patientsPI3K/AKT/mTOR activationFirst-line treatmentMetastatic breast cancerBreast cancer patientsAkt/mTOR activationMulticenter clinical trialAkt/mTORMBC patientsCancer patientsPredictive markerClinical trialsDisease progressionBreast cancerTreatment selectionTissue biopsiesPatientsNumber of FDAMTOR activation
2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2020
CDK 4/6 drug target activation mapping of HR+/HER2- metastatic breast cancer for treatment selection and response prediction.
Abu-Khalaf M, Hatzis C, Hodge K, Valdes F, Sikov W, Mita M, Denduluri N, Awerkamp K, Murphy R, Zelterman D, Dunetz B, Petricoin E, Pierobon M. CDK 4/6 drug target activation mapping of HR+/HER2- metastatic breast cancer for treatment selection and response prediction. Journal Of Clinical Oncology 2020, 38: e13029-e13029. DOI: 10.1200/jco.2020.38.15_suppl.e13029.Peer-Reviewed Original ResearchMetastatic breast cancerBreast cancerCyclin D1CDK 4/6 inhibitorsBaseline tumor tissueClass of drugsAdjuvant settingEndocrine therapyTherapy initiationFrontline therapyInhibitor therapyPFS intervalStudy treatmentPredictive markerDisease progressionClinical trialsOutcome dataTreatment selectionPathway biomarkersBiopsy materialAverage age 62Tumor tissuePatientsFinal analysisTop quartile