Browsing Breast Cancer Research by author "Linardopoulos, Spyridon"
Now showing items 1-14 of 14
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Aurora B prevents premature removal of spindle assembly checkpoint proteins from the kinetochore: A key role for Aurora B in mitosis.
Gurden, MD; Anderhub, SJ; Faisal, A; Linardopoulos, S (2018-04)Accurate chromosome segregation is dependent on the spindle assembly checkpoint (SAC). In current models, the key direct role of Aurora B in the SAC has been suggested to be to promote rapid kinetochore localisation of ... -
Aurora B prevents premature removal of spindle assembly checkpoint proteins from the kinetochore: A key role for Aurora B in mitosis.
Gurden, MD; Anderhub, SJ; Faisal, A; Linardopoulos, S (2018-04)Accurate chromosome segregation is dependent on the spindle assembly checkpoint (SAC). In current models, the key direct role of Aurora B in the SAC has been suggested to be to promote rapid kinetochore localisation of ... -
Aurora B prevents premature removal of spindle assembly checkpoint proteins from the kinetochore: A key role for Aurora B in mitosis.
Gurden, MD; Anderhub, SJ; Faisal, A; Linardopoulos, S (Impact Journals, LLC, 2018-04-13)Accurate chromosome segregation is dependent on the spindle assembly checkpoint (SAC). In current models, the key direct role of Aurora B in the SAC has been suggested to be to promote rapid kinetochore localisation of ... -
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.
Faisal, A; Mak, GWY; Gurden, MD; Xavier, CPR; Anderhub, SJ; et al. (NATURE PUBLISHING GROUP, 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 ... -
E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; et al. (AMER ASSOC CANCER RESEARCH, 2018-04-01)The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ... -
High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.
Anderhub, SJ; Mak, GW-Y; Gurden, MD; Faisal, A; Drosopoulos, K; et al. (AMER ASSOC CANCER RESEARCH, 2019-10-01)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 ... -
Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer.
Patel, N; Weekes, D; Drosopoulos, K; Gazinska, P; Noel, E; et al. (NATURE PUBLISHING GROUP, 2018-03-13)Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies ... -
Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.
Drosopoulos, K; Linardopoulos, S (2019-01)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 ... -
Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species.
Wood, FL; Shepherd, S; Hayes, A; Liu, M; Grira, K; et al. (ELSEVIER, 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 ... -
Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736.
Moore, AS; Faisal, A; Mak, GWY; Miraki-Moud, F; Bavetsias, V; et al. (ELSEVIER, 2020-04-14)Internal tandem duplication of FLT3 (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML); it causes constitutive activation of FLT3 kinase and is associated with high relapse rates and ... -
Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach.
Innocenti, P; Woodward, HL; Solanki, S; Naud, S; Westwood, IM; et al. (AMER CHEMICAL SOC, 2016-04-28)Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ... -
RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses.
Dolly, SO; Gurden, MD; Drosopoulos, K; Clarke, P; de Bono, J; et al. (NATURE PUBLISHING GROUP, 2017-09-26)BACKGROUND: F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in ... -
Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells.
Koo, C-Y; Giacomini, C; Reyes-Corral, M; Olmos, Y; Tavares, IA; et al. (AMER ASSOC CANCER RESEARCH, 2017-11-01)Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and ... -
The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.
Couty, S; Westwood, IM; Kalusa, A; Cano, C; Travers, J; et al. (IMPACT JOURNALS LLC, 2013-08-25)The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we ...