0000000001029896

AUTHOR

Ludmila Prudkin

showing 2 related works from this author

Evaluation and clinical analyses of downstream targets of the Akt inhibitor GDC-0068.

2013

Abstract Purpose: The oncogenic PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer. However, it is unknown whether the pathway blockade required for tumor growth inhibition is clinically achievable. Therefore, we conducted pharmacodynamic studies with GDC-0068, an ATP competitive, selective Akt1/2/3 inhibitor, in preclinical models and in patients treated with this compound. Experimental Design: We used a reverse phase protein array (RPPA) platform to identify a biomarker set indicative of Akt inhibition in cell lines and human-tumor xenografts, and correlated the degree of pathway inhibition with antitumor activity. Akt pathway activity was measured using this biomarker se…

MAPK/ERK pathwayCancer ResearchAKT1PharmacologyPiperazines03 medical and health sciencesMicePhosphatidylinositol 3-Kinases0302 clinical medicineIn vivoMedicineAnimalsHumansProtein kinase BProtein Kinase InhibitorsPI3K/AKT/mTOR pathway030304 developmental biology0303 health sciencesbusiness.industryTOR Serine-Threonine KinasesCancerReverse phase protein lysate microarraymedicine.diseaseXenograft Model Antitumor Assays3. Good healthOncogene Protein v-aktPyrimidinesOncology030220 oncology & carcinogenesisBiomarker (medicine)businessSignal TransductionClinical cancer research : an official journal of the American Association for Cancer Research
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A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in p…

2011

Abstract Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose. Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis…

AdultMaleCancer ResearchMaximum Tolerated Dosemedicine.medical_treatmentAntineoplastic AgentsPharmacologyAntibodies Monoclonal HumanizedDrug Administration ScheduleReceptor IGF Type 1Insulin-like growth factorPharmacokineticsNeoplasmsmedicineHumansAgedAged 80 and overDose-Response Relationship DrugDalotuzumabbusiness.industryCancerAntibodies MonoclonalMiddle Agedmedicine.diseaseOncologyTolerabilityPharmacodynamicsMonoclonalToxicityFemalebusinessClinical cancer research : an official journal of the American Association for Cancer Research
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