2015
PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling
Cheng H, Liu P, Ohlson C, Xu E, Symonds L, Isabella A, Muller WJ, Lin NU, Krop IE, Roberts TM, Winer EP, Arteaga CL, Zhao JJ. PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling. Oncogene 2015, 35: 2961-2970. PMID: 26640141, PMCID: PMC4896860, DOI: 10.1038/onc.2015.377.Peer-Reviewed Original ResearchConceptsBreast cancerPIK3CA mutationsMammary tumorsHER2 amplification/overexpressionHER2-positive breast cancerHER2-positive cancersPrimary mammary tumorsHER2/HER3PIK3CA-activating mutationsHER2/neuHuman breast cancerEffective treatment approachAmplification/overexpressionCompound mouse modelMEK-ERK signalingMouse mammary glandWorse prognosisCombination therapyMammary tumorigenesisMouse modelMutant PIK3CATreatment approachesHER2Combined inhibitionCompensatory activation
2012
Trastuzumab Emtansine (T-DM1) for the Treatment of HER2-Positive Cancer with a Focus on Breast Cancer
Rugo H, Krop I, Chu Y. Trastuzumab Emtansine (T-DM1) for the Treatment of HER2-Positive Cancer with a Focus on Breast Cancer. Cancer Drug Discovery And Development 2012, 179-210. DOI: 10.1007/978-1-4614-5456-4_11.Peer-Reviewed Original ResearchBreast cancerHER2 overexpressionHuman epidermal growth factor receptor type 2Epidermal growth factor receptor type 2Factor receptor type 2Important histopathologic featureHER2-positive cancersReceptor type 2Epidermal growth factor receptorHuman solid tumorsProgression of tumorsGrowth factor receptorHistopathologic featuresPoor prognosisOncologic unitsTrastuzumab emtansinePancreatic cancerHER receptorsSolid tumorsType 2Malignant transformationCancerTyrosine kinase familyFactor receptorSubsequent activationA phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer.
Munster P, Miller K, Krop I, Dhindsa N, Reynolds J, Geretti E, Niyikiza C, Nielsen U, Hendriks B, Wickham T, Moyo V, LoRusso P. A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer. Journal Of Clinical Oncology 2012, 30: tps663-tps663. DOI: 10.1200/jco.2012.30.15_suppl.tps663.Peer-Reviewed Original ResearchAdvanced breast cancerMaximum feasible doseBreast cancerMM-302Liposomal doxorubicinHER2-positive breast cancerTumor cellsAdequate performance statusAnthracycline-free regimensBone marrow reserveDose-escalation portionClinical benefit rateDose-limiting toxicityDose-escalation designHER2-positive cancersPreliminary efficacy dataHuman phase IStandard therapy existsBreast cancer therapyAvailable anthracyclinesPrimary endpointSecondary endpointsMarrow reservePerformance statusStandard therapyClinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer
Girish S, Gupta M, Wang B, Lu D, Krop IE, Vogel CL, Burris III HA, LoRusso PM, Yi JH, Saad O, Tong B, Chu YW, Holden S, Joshi A. Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemotherapy And Pharmacology 2012, 69: 1229-1240. PMID: 22271209, PMCID: PMC3337408, DOI: 10.1007/s00280-011-1817-3.Peer-Reviewed Original ResearchConceptsSingle-agent T-DM1Anti-therapeutic antibodiesT-DM1 exposureTotal trastuzumabT-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Standard noncompartmental approachT-DM1 pharmacokineticsGrowth factor receptor 2Key adverse eventsMetastatic breast cancerHER2-positive cancersStable thioether linkerConcentrations of transaminasesFactor receptor 2Enzyme-linked immunosorbent assayEnzyme-linked immunosorbentHER2 extracellular domainAntibody-drug conjugatesEvaluable patientsPrior therapyClinical responseAdverse events