Cancer Therapeutics
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Recent submissions
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Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.
(2017-05)Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug ... -
Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.
(2017-04-18)Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor ... -
Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma.
(2017-04-22)Targeted inhibition of Anaplastic Lymphoma Kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies, however the presence of resistant mutations necessitates both the development of more ... -
Circulating Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.
(2017-04-27)Biomarkers for a more precise patient care are needed in metastatic prostate cancer (mPC). We have reported a Phase II trial (TOPARP-A) of the poly(ADP)-ribose polymerase (PARP) inhibitor olaparib in mPC, demonstrating ... -
Pediatric high-grade glioma: biologically and clinically in need of new thinking.
(2017-02-01)High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, ... -
Targeting secondary protein complexes in drug discovery: studying the druggability and chemical biology of the HSP70/BAG1 complex.
(2017-05-04)Proteins typically carry out their biological functions as multi-protein complexes, which can significantly affect the affinity of small-molecule inhibitors. HSP70 is an important target in oncology, so to study its chemical ... -
Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma.
(2017-05-08)To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed ... -
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.
(2017-04-25)BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ... -
Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.
(2017-03-31)Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly ... -
An Irreversible Inhibitor of HSP72 that Unexpectedly Targets Lysine-56.
(2017-03-20)The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells ... -
MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma.
(2016-11-22)BACKGROUND: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease ... -
Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.
(2017-01)Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality ... -
Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.
(2016-11-29)Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ... -
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.
(2016-09-28)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, WX-554, ... -
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.
(2017-06)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.
(2017)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 ...
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