Cancer Therapeutics
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Recent submissions
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High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.
(2019-10)BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly ... -
Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species.
(2019-11-01)CCT241736 is a dual fms-like tyrosine kinase 3 (FLT3)/Aurora kinase inhibitor in development for the treatment of acute myeloid leukaemia. The successful development of any new drug relies on adequate safety testing including ... -
A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations.
(2019-09-11)BACKGROUND: For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed. METHODS: We have developed a hybrid-capture next-generation ... -
In vivo modelling of chemo-resistant neuroblastoma provides new insights into chemo-refractory disease and metastasis.
(2019-08-12)Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant in vivo models has limited our insight into the development ... -
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
(2016-05)Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ... -
Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Non-invasive Magnetic Resonance Elastography.
(2019-10-11)Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic ... -
De novo phosphatidylcholine synthesis is required for autophagosome membrane formation and maintenance during autophagy.
(2019-09-13)Macroautophagy/autophagy can enable cancer cells to withstand cellular stress and maintain bioenergetic homeostasis by sequestering cellular components into newly formed double-membrane vesicles destined for lysosomal ... -
History of the Selective Autophagy Research: How Did It Begin and Where Does It Stand Today?
(2019-05-11)Autophagy, self-eating, is a pivotal catabolic mechanism that ensures homeostasis and survival of the cell in the face of stressors as different as starvation, infection, or protein misfolding. The importance of the research ... -
A phase I study to assess afatinib in combination with carboplatin or with carboplatin plus paclitaxel in patients with advanced solid tumors.
(2018-11)PURPOSE: Afatinib, an irreversible ErbB family blocker, has demonstrated preclinical antitumor activity with chemotherapy. METHODS: As part of a phase I trial in patients with advanced solid tumors (NCT00809133; 3 + 3 ... -
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 ...
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