Recent submissions
Now showing items 581-600 of 658
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A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours.
(ELSEVIER SCI LTD, 2016-11-01)PURPOSE: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, ... -
A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.
(WILEY, 2017-06-01)Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and ... -
Assessing histone demethylase inhibitors in cells: lessons learned.
(BIOMED CENTRAL LTD, 2017-03-01)BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ... -
Immuno-oncology combinations: raising the tail of the survival curve.
(2016-06)There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small ... -
Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit.
(ELSEVIER SCI LTD, 2017-04-01)BACKGROUND: We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection ... -
Applications of Systematic Molecular Scaffold Enumeration to Enrich Structure-Activity Relationship Information.
(2017-01)Establishing structure-activity relationships (SARs) in hit identification during early stage drug discovery is important in accelerating hit confirmation and expansion. We describe the development of EnCore, a systematic ... -
Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics.
(2017-01)Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize treatment efficacy and ... -
Development of molecularly targeted agents and immunotherapies in small cell lung cancer.
(ELSEVIER SCI LTD, 2016-06-01)Small cell lung cancer (SCLC) is a smoking-induced malignancy with multiple toxin-associated mutations, which accounts for 15% of all lung cancers. It remains a clinical challenge with a rapid doubling time, early dissemination ... -
Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2016-09-01)Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents ... -
Emerging biomarkers for PD-1 pathway cancer therapy.
(2017-01)The field of immuno-oncology has witnessed unprecedented success in recent years, with several PD=1 and PD-L1 inhibitors obtaining US FDA registration and breakthrough drug therapy designation in multiple tumor types. ... -
Emerging strategies for the treatment of advanced small cell lung cancer.
(AME PUBLISHING COMPANY, 2016-10-01) -
Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.
(OXFORD UNIV PRESS, 2017-02-23)BACKGROUND: Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but ... -
Copy Number Profiling of Brazilian Astrocytomas.
(OXFORD UNIV PRESS INC, 2016-07-07)Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of ... -
Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.
(MASSACHUSETTS MEDICAL SOC, 2016-08-04)BACKGROUND: Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized ... -
Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.
(SPRINGER, 2017-04-01)Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in ... -
Mapping the 3D structures of small molecule binding sites
(BMC, 2016-12-06) -
Chemical approaches to targeted protein degradation through modulation of the ubiquitin-proteasome pathway.
(PORTLAND PRESS LTD, 2017-03-15)Manipulation of the ubiquitin-proteasome system to achieve targeted degradation of proteins within cells using chemical tools and drugs has the potential to transform pharmacological and therapeutic approaches in cancer ... -
Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.
(NATURE PUBLISHING GROUP, 2016-12-09)We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary ... -
Maximising the potential of AKT inhibitors as anti-cancer treatments.
(PERGAMON-ELSEVIER SCIENCE LTD, 2017-04-01)PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly ... -
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
(AMER CHEMICAL SOC, 2016-12-16)The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ...