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PURPOSE AKT signaling is frequently deregulated in human cancers. MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms with antitumor activity in preclinical models. A phase I study of MK-2206 was conducted to investigate its safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics (PDs), and preliminary antitumor(More)
A dose-escalation, phase I study evaluated the safety, pharmacokinetics, pharmacogenomics, and efficacy of ES-285, a novel agent isolated from a marine mollusc, in adult cancer patients. Patients received a 24-hour i.v. infusion of ES-285 once every 3 weeks until disease progression or unacceptable toxicity. The starting dose was 4 mg/m(2). Dose escalation(More)
PURPOSE This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K). PATIENTS AND(More)
3037^ Background: AKT is a key regulator of cellular proliferation, apoptosis and growth. A range of cancers have genetic aberrations that involve the PI3K/AKT pathway, leading to abnormal AKT hyperactivation and tumor progression. MK-2206 is a novel potent investigational AKT inhibitor, which was initially administered orally in a QOD schedule, where the(More)
A 69-year-old woman, who had suffered from deforming rheumatoid arthritis since the age of 40 years, had been treated with methotrexate for 3 years. She presented with a 7 week history of neck lymphadenopathy. Biopsy revealed low-grade marginal-zone B-cell non-Hodgkin's lymphoma. Computerized tomography and bone marrow biopsy confirmed stage IIIA disease.(More)
The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preserved through passaging in the mouse. An integrated platform(More)
BACKGROUND Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tolerability, maximum tolerated dose,(More)
Clinical drug resistance is a major barrier to overcome before chemotherapy can become curative for most patients presenting with metastatic cancer. Rational attempts to tackle clinical drug resistance need to be based on an understanding of the mechanisms involved; these are likely to be complex and multifactorial, and may be due to inadequate drug(More)
PURPOSE Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. (More)
Continued cultivation of vaccine virus in a medium consisting of minced chick embryo tissue and Tyrode's solution has resulted in a virus qualitatively changed to such an extent that considerable amounts of it can be injected intradermally into human beings without danger or inconvenience. Individuals who are vaccinated intradermally with the cultured virus(More)