Browsing by author "Clarke, Paul"
Now showing items 21-32 of 32
-
Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling.
Bright, MD; Clarke, PA; Workman, P; Davies, FE (ELSEVIER SCIENCE INC, 2018-04-01)Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. ... -
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
Poon, E; Liang, T; Jamin, Y; Walz, S; Kwok, C; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2020-11-02)The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ... -
Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.
Pawlyn, C; Bright, MD; Buros, AF; Stein, CK; Walters, Z; et al. (SPRINGERNATURE, 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 ... -
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ... -
Pediatric and adult glioblastoma radiosensitization induced by PI3K/mTOR inhibition causes early metabolic alterations detected by nuclear magnetic resonance spectroscopy.
Agliano, A; Balarajah, G; Ciobota, DM; Sidhu, J; Clarke, PA; et al. (IMPACT JOURNALS LLC, 2017-07-18)Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. ... -
Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.
Smith, JR; de Billy, E; Hobbs, S; Powers, M; Prodromou, C; et al. (NATURE PUBLISHING GROUP, 2015-01-02)The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key ... -
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 ... -
Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases.
Zhang, C; Stockwell, SR; Elbanna, M; Ketteler, R; Freeman, J; et al. (NATURE PUBLISHING GROUP, 2019-07-25)Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on ... -
Small-molecule targeting of brachyury transcription factor addiction in chordoma.
Sharifnia, T; Wawer, MJ; Chen, T; Huang, Q-Y; Weir, BA; et al. (2019-02)Chordoma is a primary bone cancer with no approved therapy 1 . The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in ... -
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
Czodrowski, P; Mallinger, A; Wienke, D; Esdar, C; Pöschke, O; et al. (AMER CHEMICAL SOC, 2016-10-27)The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ... -
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 ... -
The kinase polypharmacology landscape of clinical PARP inhibitors.
Antolin, AA; Ameratunga, M; Banerji, U; Clarke, PA; Workman, P; et al. (NATURE PUBLISHING GROUP, 2020-02-17)Polypharmacology plays an important role in defining response and adverse effects of drugs. For some mechanisms, experimentally mapping polypharmacology is commonplace, although this is typically done within the same protein ...