CORE
🇺🇦
make metadata, not war
Services
Services overview
Explore all CORE services
Access to raw data
API
Dataset
FastSync
Content discovery
Recommender
Discovery
OAI identifiers
OAI Resolver
Managing content
Dashboard
Bespoke contracts
Consultancy services
Support us
Support us
Membership
Sponsorship
Community governance
Advisory Board
Board of supporters
Research network
About
About us
Our mission
Team
Blog
FAQs
Contact us
research
3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors
Authors
Alexander M. Reece-Smith
Andrew J. McKenzie
+17 more
Anna M. Grabowska
Anne
Brett M. Hall
David Onion
Dileep N. Lobo
Ettinger
Hari L. Ratan
John C. Atherton
John P. Duffy
Madeleine L. Craze
Perez-Soler
Peter King
Philip A. Clarke
Rajendra Kumari
Richard H. Argent
Robert G. Pineda
Simon L. Parsons
Publication date
1 April 2016
Publisher
'American Association for Cancer Research (AACR)'
Doi
Cite
Abstract
There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR
Similar works
Full text
Open in the Core reader
Download PDF
Available Versions
Name not available
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:eprints.nottingham.ac.uk:4...
Last time updated on 14/12/2017
Nottingham ePrints
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:eprints.nottingham.ac.uk:4...
Last time updated on 16/02/2017
Crossref
See this paper in CORE
Go to the repository landing page
Download from data provider
info:doi/10.1158%2F1535-7163.m...
Last time updated on 01/04/2019
Name not available
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:eprints.nottingham.ac.uk:4...
Last time updated on 14/12/2017
Nottingham eTheses
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:eprints.nottingham.ac.uk:4...
Last time updated on 07/01/2023
Repository@Nottingham
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:nottingham-repository.work...
Last time updated on 08/01/2019