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Targeting castration-resistant prostate cancer with androgen receptor antisense oligonucleotide therapy.

De Velasco MA, Kura Y, Sakai K, Hatanaka Y, Davies BR, Campbell H, Klein S, Kim Y, MacLeod AR, Sugimoto K, Yoshikawa K, Nishio K, Uemura H.

JCI Insight. 2019 Sep 5;4(17). pii: 122688. doi: 10.1172/jci.insight.122688.


BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population.

Turner NC, Alarcón E, Armstrong AC, Philco M, López Chuken YA, Sablin MP, Tamura K, Gómez Villanueva A, Pérez-Fidalgo JA, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Foxley A, Lindemann JPO, Maudsley R, Moschetta M, Outhwaite E, Pass M, Rugman P, Schiavon G, Oliveira M.

Ann Oncol. 2019 May 1;30(5):774-780. doi: 10.1093/annonc/mdz086.


Frailty assessment in primary health care and its association with unplanned secondary care use: a rapid review.

Davies BR, Baxter H, Rooney J, Simons P, Sephton A, Purdy S, Huntley AL.

BJGP Open. 2018 Apr 10;2(1):bjgpopen18X101325. doi: 10.3399/bjgpopen18X101325. eCollection 2018 Apr.


Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor β Superfamily Type 1 Receptors.

Spender LC, Ferguson GJ, Hughes GD, Davies BR, Goldberg FW, Herrera B, Taylor RG, Strathearn LS, Sansom OJ, Barry ST, Inman GJ.

Mol Pharmacol. 2019 Feb;95(2):222-234. doi: 10.1124/mol.118.112946. Epub 2018 Nov 20.


Optimizing the design of population-based patient-derived tumor xenograft studies to better predict clinical response.

Floc'h N, Guerriero ML, Ramos-Montoya A, Davies BR, Cairns J, Karp NA.

Dis Model Mech. 2018 Oct 31;11(11). pii: dmm036160. doi: 10.1242/dmm.036160.


Delineating the distinct role of AKT in mediating cell survival and proliferation induced by CD154 and IL-4/IL-21 in chronic lymphocytic leukemia.

Chapman EA, Oates M, Mohammad IS, Davies BR, Stockman PK, Zhuang J, Pettitt AR.

Oncotarget. 2017 Nov 7;8(61):102948-102964. doi: 10.18632/oncotarget.22292. eCollection 2017 Nov 28.


Akt inhibition improves long-term tumour control following radiotherapy by altering the microenvironment.

Searle EJ, Telfer BA, Mukherjee D, Forster DM, Davies BR, Williams KJ, Stratford IJ, Illidge TM.

EMBO Mol Med. 2017 Dec;9(12):1646-1659. doi: 10.15252/emmm.201707767.


A Phase I Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor AZD5363 for Evaluation in Solid Tumors and in PIK3CA-Mutated Breast and Gynecologic Cancers.

Banerji U, Dean EJ, Pérez-Fidalgo JA, Batist G, Bedard PL, You B, Westin SN, Kabos P, Garrett MD, Tall M, Ambrose H, Barrett JC, Carr TH, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Elvin P, Foxley A, Lawrence P, Lindemann JPO, Maudsley R, Pass M, Rowlands V, Rugman P, Schiavon G, Yates J, Schellens JHM.

Clin Cancer Res. 2018 May 1;24(9):2050-2059. doi: 10.1158/1078-0432.CCR-17-2260. Epub 2017 Oct 24.


Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer.

Butler DE, Marlein C, Walker HF, Frame FM, Mann VM, Simms MS, Davies BR, Collins AT, Maitland NJ.

Oncotarget. 2017 May 23;8(34):56698-56713. doi: 10.18632/oncotarget.18082. eCollection 2017 Aug 22.


A pharmacokinetic-pharmacodynamic model predicting tumour growth inhibition after intermittent administration with the mTOR kinase inhibitor AZD8055.

Yates JWT, Holt SV, Logie A, Payne K, Woods K, Wilkinson RW, Davies BR, Guichard SM.

Br J Pharmacol. 2017 Aug;174(16):2652-2661. doi: 10.1111/bph.13886. Epub 2017 Jul 6.


Annual hospitalization rates for children with asthma are inversely associated with total hours of sunshine in English regions.

Davies BR, Gilchrist FJ, Saunders A, Carroll WD.

Clin Exp Allergy. 2017 Jun;47(6):838-840. doi: 10.1111/cea.12946. No abstract available.


Trauma and homelessness in youth: Psychopathology and intervention.

Davies BR, Allen NB.

Clin Psychol Rev. 2017 Jun;54:17-28. doi: 10.1016/j.cpr.2017.03.005. Epub 2017 Mar 24. Review.


Sensitivity to PI3K and AKT inhibitors is mediated by divergent molecular mechanisms in subtypes of DLBCL.

Erdmann T, Klener P, Lynch JT, Grau M, Vočková P, Molinsky J, Tuskova D, Hudson K, Polanska UM, Grondine M, Mayo M, Dai B, Pfeifer M, Erdmann K, Schwammbach D, Zapukhlyak M, Staiger AM, Ott G, Berdel WE, Davies BR, Cruzalegui F, Trneny M, Lenz P, Barry ST, Lenz G.

Blood. 2017 Jul 20;130(3):310-322. doi: 10.1182/blood-2016-12-758599. Epub 2017 Feb 15.


Combination treatment of prostate cancer with FGF receptor and AKT kinase inhibitors.

Feng S, Shao L, Castro P, Coleman I, Nelson PS, Smith PD, Davies BR, Ittmann M.

Oncotarget. 2017 Jan 24;8(4):6179-6192. doi: 10.18632/oncotarget.14049.


Identification of Pharmacodynamic Transcript Biomarkers in Response to FGFR Inhibition by AZD4547.

Delpuech O, Rooney C, Mooney L, Baker D, Shaw R, Dymond M, Wang D, Zhang P, Cross S, Veldman-Jones M, Wilson J, Davies BR, Dry JR, Kilgour E, Smith PD.

Mol Cancer Ther. 2016 Nov;15(11):2802-2813. Epub 2016 Aug 22.


Identification of differential PI3K pathway target dependencies in T-cell acute lymphoblastic leukemia through a large cancer cell panel screen.

Lynch JT, McEwen R, Crafter C, McDermott U, Garnett MJ, Barry ST, Davies BR.

Oncotarget. 2016 Apr 19;7(16):22128-39. doi: 10.18632/oncotarget.8031.


Efficacy of targeted AKT inhibition in genetically engineered mouse models of PTEN-deficient prostate cancer.

De Velasco MA, Kura Y, Yoshikawa K, Nishio K, Davies BR, Uemura H.

Oncotarget. 2016 Mar 29;7(13):15959-76. doi: 10.18632/oncotarget.7557.


Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma.

Ezell SA, Wang S, Bihani T, Lai Z, Grosskurth SE, Tepsuporn S, Davies BR, Huszar D, Byth KF.

Oncotarget. 2016 Feb 23;7(8):9163-74. doi: 10.18632/oncotarget.7036.


A New Raman Metric for the Characterisation of Graphene oxide and its Derivatives.

King AA, Davies BR, Noorbehesht N, Newman P, Church TL, Harris AT, Razal JM, Minett AI.

Sci Rep. 2016 Jan 18;6:19491. doi: 10.1038/srep19491.


Production of Highly Monolayer Enriched Dispersions of Liquid-Exfoliated Nanosheets by Liquid Cascade Centrifugation.

Backes C, Szydłowska BM, Harvey A, Yuan S, Vega-Mayoral V, Davies BR, Zhao PL, Hanlon D, Santos EJ, Katsnelson MI, Blau WJ, Gadermaier C, Coleman JN.

ACS Nano. 2016 Jan 26;10(1):1589-601. doi: 10.1021/acsnano.5b07228. Epub 2016 Jan 12.


Bespoke video vignettes - an approach to enhancing reflective learning developed by dental undergraduates and their clinical teachers.

Davies BR, Leung AN, Dunne SM, Dillon J, Blum IR.

Eur J Dent Educ. 2017 Feb;21(1):33-36. doi: 10.1111/eje.12175. Epub 2015 Nov 17.


AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules.

Guichard SM, Curwen J, Bihani T, D'Cruz CM, Yates JW, Grondine M, Howard Z, Davies BR, Bigley G, Klinowska T, Pike KG, Pass M, Chresta CM, Polanska UM, McEwen R, Delpuech O, Green S, Cosulich SC.

Mol Cancer Ther. 2015 Nov;14(11):2508-18. doi: 10.1158/1535-7163.MCT-15-0365. Epub 2015 Sep 10.


Tumors with AKT1E17K Mutations Are Rational Targets for Single Agent or Combination Therapy with AKT Inhibitors.

Davies BR, Guan N, Logie A, Crafter C, Hanson L, Jacobs V, James N, Dudley P, Jacques K, Ladd B, D'Cruz CM, Zinda M, Lindemann J, Kodaira M, Tamura K, Jenkins EL.

Mol Cancer Ther. 2015 Nov;14(11):2441-51. doi: 10.1158/1535-7163.MCT-15-0230. Epub 2015 Sep 8.


Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

O'Neill D, Jones D, Wade M, Grey J, Nakjang S, Guo W, Cork D, Davies BR, Wedge SR, Robson CN, Gaughan L.

Oncotarget. 2015 Sep 22;6(28):26029-40. doi: 10.18632/oncotarget.4347.


AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo.

Ribas R, Pancholi S, Guest SK, Marangoni E, Gao Q, Thuleau A, Simigdala N, Polanska UM, Campbell H, Rani A, Liccardi G, Johnston S, Davies BR, Dowsett M, Martin LA.

Mol Cancer Ther. 2015 Sep;14(9):2035-48. doi: 10.1158/1535-7163.MCT-15-0143. Epub 2015 Jun 26.


Combining AZD8931, a novel EGFR/HER2/HER3 signalling inhibitor, with AZD5363 limits AKT inhibitor induced feedback and enhances antitumour efficacy in HER2-amplified breast cancer models.

Crafter C, Vincent JP, Tang E, Dudley P, James NH, Klinowska T, Davies BR.

Int J Oncol. 2015 Aug;47(2):446-54. doi: 10.3892/ijo.2015.3062. Epub 2015 Jun 22.


Validation of a predictive modeling approach to demonstrate the relative efficacy of three different schedules of the AKT inhibitor AZD5363.

Yates JW, Dudley P, Cheng J, D'Cruz C, Davies BR.

Cancer Chemother Pharmacol. 2015 Aug;76(2):343-56. doi: 10.1007/s00280-015-2795-7. Epub 2015 Jun 20.


Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel.

Hancox U, Cosulich S, Hanson L, Trigwell C, Lenaghan C, Ellston R, Dry H, Crafter C, Barlaam B, Fitzek M, Smith PD, Ogilvie D, D'Cruz C, Castriotta L, Wedge SR, Ward L, Powell S, Lawson M, Davies BR, Harrington EA, Foster E, Cumberbatch M, Green S, Barry ST.

Mol Cancer Ther. 2015 Jan;14(1):48-58. doi: 10.1158/1535-7163.MCT-14-0406. Epub 2014 Nov 14.


High Efficacy of Combination Therapy Using PI3K/AKT Inhibitors with Androgen Deprivation in Prostate Cancer Preclinical Models.

Marques RB, Aghai A, de Ridder CMA, Stuurman D, Hoeben S, Boer A, Ellston RP, Barry ST, Davies BR, Trapman J, van Weerden WM.

Eur Urol. 2015 Jun;67(6):1177-1185. doi: 10.1016/j.eururo.2014.08.053. Epub 2014 Sep 12.


Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase.

Fu X, Creighton CJ, Biswal NC, Kumar V, Shea M, Herrera S, Contreras A, Gutierrez C, Wang T, Nanda S, Giuliano M, Morrison G, Nardone A, Karlin KL, Westbrook TF, Heiser LM, Anur P, Spellman P, Guichard SM, Smith PD, Davies BR, Klinowska T, Lee AV, Mills GB, Rimawi MF, Hilsenbeck SG, Gray JW, Joshi A, Osborne CK, Schiff R.

Breast Cancer Res. 2014 Sep 11;16(5):430. doi: 10.1186/s13058-014-0430-x.


Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models.

Toren P, Kim S, Cordonnier T, Crafter C, Davies BR, Fazli L, Gleave ME, Zoubeidi A.

Eur Urol. 2015 Jun;67(6):986-990. doi: 10.1016/j.eururo.2014.08.006. Epub 2014 Aug 20.


PIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways.

Meja K, Stengel C, Sellar R, Huszar D, Davies BR, Gale RE, Linch DC, Khwaja A.

Br J Haematol. 2014 Oct;167(1):69-79. doi: 10.1111/bjh.13013. Epub 2014 Jun 30.


The triglyceride to high-density lipoprotein ratio identifies children who may be at risk of developing cardiometabolic disease.

Bailey DP, Savory LA, Denton SJ, Davies BR, Kerr CJ.

Acta Paediatr. 2014 Aug;103(8):e349-53. doi: 10.1111/apa.12677. Epub 2014 May 21.


The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer, and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to Taxotere.

Li J, Davies BR, Han S, Zhou M, Bai Y, Zhang J, Xu Y, Tang L, Wang H, Liu YJ, Yin X, Ji Q, Yu DH.

J Transl Med. 2013 Oct 2;11:241. doi: 10.1186/1479-5876-11-241.


Synergistic targeting of PI3K/AKT pathway and androgen receptor axis significantly delays castration-resistant prostate cancer progression in vivo.

Thomas C, Lamoureux F, Crafter C, Davies BR, Beraldi E, Fazli L, Kim S, Thaper D, Gleave ME, Zoubeidi A.

Mol Cancer Ther. 2013 Nov;12(11):2342-55. doi: 10.1158/1535-7163.MCT-13-0032. Epub 2013 Aug 21.


Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors.

Sommer EM, Dry H, Cross D, Guichard S, Davies BR, Alessi DR.

Biochem J. 2013 Jun 15;452(3):499-508. doi: 10.1042/BJ20130342.


Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases.

Addie M, Ballard P, Buttar D, Crafter C, Currie G, Davies BR, Debreczeni J, Dry H, Dudley P, Greenwood R, Johnson PD, Kettle JG, Lane C, Lamont G, Leach A, Luke RW, Morris J, Ogilvie D, Page K, Pass M, Pearson S, Ruston L.

J Med Chem. 2013 Mar 14;56(5):2059-73. doi: 10.1021/jm301762v. Epub 2013 Feb 26.


An act of faith.

Davies BR.

Br Dent J. 2013 Feb;214(3):95. doi: 10.1038/sj.bdj.2013.116. No abstract available.


2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography demonstrates target inhibition with the potential to predict anti-tumour activity following treatment with the AKT inhibitor AZD5363.

Maynard J, Ricketts SA, Gendrin C, Dudley P, Davies BR.

Mol Imaging Biol. 2013 Aug;15(4):476-85. doi: 10.1007/s11307-013-0613-3.


Blocked autophagy using lysosomotropic agents sensitizes resistant prostate tumor cells to the novel Akt inhibitor AZD5363.

Lamoureux F, Thomas C, Crafter C, Kumano M, Zhang F, Davies BR, Gleave ME, Zoubeidi A.

Clin Cancer Res. 2013 Feb 15;19(4):833-44. doi: 10.1158/1078-0432.CCR-12-3114. Epub 2012 Dec 20.


The hypertriglyceridemic waist, waist-to-height ratio, and cardiometabolic risk.

Bailey DP, Savory LA, Denton SJ, Davies BR, Kerr CJ.

J Pediatr. 2013 Apr;162(4):746-52. doi: 10.1016/j.jpeds.2012.09.051. Epub 2012 Nov 6.


Autophagy limits the cytotoxic effects of the AKT inhibitor AZ7328 in human bladder cancer cells.

Dickstein RJ, Nitti G, Dinney CP, Davies BR, Kamat AM, McConkey DJ.

Cancer Biol Ther. 2012 Nov;13(13):1325-38. doi: 10.4161/cbt.21793. Epub 2012 Aug 16.


The MEK1/2 inhibitor, selumetinib (AZD6244; ARRY-142886), enhances anti-tumour efficacy when combined with conventional chemotherapeutic agents in human tumour xenograft models.

Holt SV, Logié A, Odedra R, Heier A, Heaton SP, Alferez D, Davies BR, Wilkinson RW, Smith PD.

Br J Cancer. 2012 Feb 28;106(5):858-66. doi: 10.1038/bjc.2012.8. Epub 2012 Feb 16.


Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background.

Davies BR, Greenwood H, Dudley P, Crafter C, Yu DH, Zhang J, Li J, Gao B, Ji Q, Maynard J, Ricketts SA, Cross D, Cosulich S, Chresta CC, Page K, Yates J, Lane C, Watson R, Luke R, Ogilvie D, Pass M.

Mol Cancer Ther. 2012 Apr;11(4):873-87. doi: 10.1158/1535-7163.MCT-11-0824-T. Epub 2012 Jan 31.


Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055).

Holt SV, Logie A, Davies BR, Alferez D, Runswick S, Fenton S, Chresta CM, Gu Y, Zhang J, Wu YL, Wilkinson RW, Guichard SM, Smith PD.

Cancer Res. 2012 Apr 1;72(7):1804-13. doi: 10.1158/0008-5472.CAN-11-1780. Epub 2012 Jan 23.


Diverse heterocyclic scaffolds as allosteric inhibitors of AKT.

Kettle JG, Brown S, Crafter C, Davies BR, Dudley P, Fairley G, Faulder P, Fillery S, Greenwood H, Hawkins J, James M, Johnson K, Lane CD, Pass M, Pink JH, Plant H, Cosulich SC.

J Med Chem. 2012 Feb 9;55(3):1261-73. doi: 10.1021/jm201394e. Epub 2012 Jan 27.


Two major patterns of nongenetic malformations are found at autopsy.

Davies BR, Giménez-Scherer JA.

Pediatr Dev Pathol. 2011 May-Jun;14(3):206-13. doi: 10.2350/10-02-0797-OA.1. Epub 2010 Nov 24.


The use of inhaled corticosteroids in the wheezy under 5-year-old child.

Davies BR, Carroll WD.

Arch Dis Child Educ Pract Ed. 2011 Apr;96(2):61-6. doi: 10.1136/adc.2009.171272. Epub 2010 Jul 30. Review.


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