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Titration of signalling output: insights into clinical combinations of MEK and AKT inhibitors.
(OXFORD UNIV PRESS, 2015-07-01)
BACKGROUND: We aimed to understand the relative contributions of inhibiting MEK and AKT on cell growth to guide combinations of these agents. MATERIALS AND METHODS: A panel of 20 cell lines was exposed to either the MEK ...
First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014.
(AMER ASSOC CANCER RESEARCH, 2015-08-01)
PURPOSE: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and in vivo efficacy across a range of preclinical human cancer models. EXPERIMENTAL DESIGN: A rolling six-dose escalation was performed to ...
Antibody-drug conjugates--an emerging class of cancer treatment.
(NATURE PUBLISHING GROUP, 2016-02-16)
Antibody-drug conjugates (ADCs) are an emerging novel class of anticancer treatment agents that combines the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs. New linker technology associated ...
Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
(AMER ASSOC CANCER RESEARCH, 2016-06-01)
PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and ...
Application of Liquid Biopsies in Cancer Targeted Therapy.
(WILEY, 2017-11-01)
As a growing body of evidence demonstrates intertumoral and intratumoral heterogeneity and clonal evolution, both during carcinogenesis and also throughout treatment resulting in acquired drug resistance, the utility of ...
AKT Inhibition in Solid Tumors With AKT1 Mutations.
(AMER SOC CLINICAL ONCOLOGY, 2017-07-10)
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary ...
Combine and conquer: challenges for targeted therapy combinations in early phase trials.
(NATURE PUBLISHING GROUP, 2017-01-01)
Our increasing understanding of cancer biology has led to the development of molecularly targeted anticancer drugs. The full potential of these agents has not, however, been realised, owing to the presence of de novo ...
Empowerment in adolescents and young adults with cancer: Relationship with health-related quality of life.
(WILEY, 2017-10-15)
BACKGROUND: The difficulties adolescents and young adults (AYAs) encounter during a cancer experience may result in a reduction in or absence of empowerment. The aims of the current study were to assess levels of empowerment ...
Young adults: a unique group in cancer epidemiological research.
(ELSEVIER SCIENCE INC, 2018-02-01)
Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
(CELL PRESS, 2017-04-18)
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We ...