Cancer Therapeutics
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Recent submissions
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Spatially constrained tumour growth affects the patterns of clonal selection and neutral drift in cancer genomic data.
(2019-07)Quantification of the effect of spatial tumour sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumour growth ... -
Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.
(2019-04-27)BACKGROUND: Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies ... -
Genomic correlates of clinical outcome in advanced prostate cancer.
(2019-06-04)Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about the impact of this heterogeneity on clinical outcome. Here, ... -
Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
(2019-08)It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ... -
Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study.
(2019-08)BACKGROUND: Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour ... -
Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer.
(2018-12)BACKGROUND: Loss of ataxia telangiectasia mutated (ATM), a key protein regulating DNA repair signaling, has been suggested to increase sensitivity to DNA damaging agents. We conducted a study analyzing the loss of ATM ... -
Development and validation of a LC-MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma.
(2017-07)AIM: SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated. METHODS & RESULTS: ... -
Catalytic inhibition of KDM1A in Ewing sarcoma is insufficient as a therapeutic strategy.
(2019-09)BACKGROUND: Ewing sarcoma and desmoplastic small round cell tumors (DSRCT) are rare and clinically aggressive sarcomas usually characterized by oncogenic fusion proteins involving EWS. Emerging studies of Ewing sarcoma ... -
The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models.
(2019-05-28)Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic ... -
Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.
(2019)Cellular models for siRNA and small molecule high-throughput screening have been widely used in the last decade to identify targets for drug discovery. As an example, we present a twofold readout approach based on cell ... -
Multidisciplinary interventions in a specialist Drug Development Unit to improve family history documentation and onward referral of patients with advanced cancer to cancer genetics services.
(2019-06)BACKGROUND: Molecular aberrations in cancer may represent therapeutic targets, and, if arising from the germline, may impact further cancer risk management in patients and their blood relatives. Annually, 600-700 patients ... -
Interlaboratory Reproducibility of a Targeted Metabolomics Platform for Analysis of Human Serum and Plasma.
(2017-01-03)A critical question facing the field of metabolomics is whether data obtained from different centers can be effectively compared and combined. An important aspect of this is the interlaboratory precision (reproducibility) ... -
ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.
(2019)Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug ... -
Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females.
(2019-03-30)Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the ... -
An atypical LIR motif within UBA5 (ubiquitin like modifier activating enzyme 5) interacts with GABARAP proteins and mediates membrane localization of UBA5.
(2019-04-16)Short linear motifs, known as LC3-interacting regions (LIRs), interact with mactoautophagy/autophagy modifiers (Atg8/LC3/GABARAP proteins) via a conserved universal mechanism. Typically, this includes the occupancy of 2 ... -
Circulating tumour cell increase as a biomarker of disease progression in metastatic castration-resistant prostate cancer patients with low baseline CTC counts.
(2018-07-01)Background: The development of treatment response and surrogate biomarkers for advanced prostate cancer care is an unmet clinical need. Patients with baseline circulating tumour cell (BLCTCs) counts <5/7.5 mL represent a ... -
Genomic Analysis of Three Metastatic Prostate Cancer Patients with Exceptional Responses to Carboplatin Indicating Different Types of DNA Repair Deficiency.
(2019-01)Platinum-based regimens have not been proved to increase survival from advanced prostate cancer (PCa). Incontrovertible evidence that a proportion of prostate cancers have homologous recombination DNA (HRD) repair defects, ... -
Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer.
(2019-01-02)BACKGROUND: Liquid biopsies have demonstrated that the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced response and overall survival from endocrine therapies in castration-resistant ...
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