Proliferation and AKT Activity Biomarker Analyses after Capivasertib (AZD5363) Treatment of Patients with ER


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 04 2020
Historique:
received: 18 09 2019
revised: 22 11 2019
accepted: 10 12 2019
pubmed: 15 12 2019
medline: 23 1 2021
entrez: 15 12 2019
Statut: ppublish

Résumé

The STAKT study examined short-term exposure (4.5 days) to the oral selective pan-AKT inhibitor capivasertib (AZD5363) to determine if this drug can reach its therapeutic target in sufficient concentration to significantly modulate key biomarkers of the AKT pathway and tumor proliferation. STAKT was a two-stage, double-blind, randomized, placebo-controlled, "window-of-opportunity" study in patients with newly diagnosed ER After 4.5 days' exposure, capivasertib 480 mg b.i.d. ( Capivasertib 480 mg b.i.d. rapidly modulates key biomarkers of the AKT pathway and decreases proliferation marker Ki67, suggesting future potential as an effective therapy in AKT-dependent breast cancers.

Identifiants

pubmed: 31836609
pii: 1078-0432.CCR-19-3053
doi: 10.1158/1078-0432.CCR-19-3053
doi:

Substances chimiques

Biomarkers, Tumor 0
ESR1 protein, human 0
Estrogen Receptor alpha 0
Ki-67 Antigen 0
MKI67 protein, human 0
Protein Kinase Inhibitors 0
Pyrimidines 0
Pyrroles 0
AKT1 protein, human EC 2.7.11.1
Proto-Oncogene Proteins c-akt EC 2.7.11.1
capivasertib WFR23M21IE

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1574-1585

Subventions

Organisme : Cancer Research UK
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

John F R Robertson (JFR)

University of Nottingham, Nottingham, UK. john.robertson@nottingham.ac.uk.

Robert E Coleman (RE)

University of Sheffield, Sheffield, UK.

Kwok-Leung Cheung (KL)

University of Nottingham, Royal Derby Hospital Centre, Derby, UK.

Abigail Evans (A)

Poole Hospital NHS Foundation Trust, Poole, UK.

Chris Holcombe (C)

Royal Liverpool University Hospital, Liverpool, UK.

Anthony Skene (A)

Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, UK.

Daniel Rea (D)

University of Birmingham, Birmingham, UK.

Samreen Ahmed (S)

Leicester Royal Infirmary, Leicester, UK.

Ali Jahan (A)

King's Mill Hospital, Nottingham, UK.

Kieran Horgan (K)

Leeds General Infirmary, Leeds, UK.

Petra Rauchhaus (P)

University of Dundee, Dundee, UK.

Roberta Littleford (R)

University of Dundee, Dundee, UK.

S Y Amy Cheung (SYA)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Marie Cullberg (M)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Elza C de Bruin (EC)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Loumpiana Koulai (L)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Justin P O Lindemann (JPO)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Martin Pass (M)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Paul Rugman (P)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Gaia Schiavon (G)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Rahul Deb (R)

Department of Histopathology, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK.

Pauline Finlay (P)

Cardiff University, Cardiff, UK.

Andrew Foxley (A)

IMED Biotech Unit, AstraZeneca, Cambridge, UK.

Julia M W Gee (JMW)

Cardiff University, Cardiff, UK.

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Classifications MeSH