当前位置： SCI文献检索 > MOLECULAR CANCER THERAPEUTICS期刊下所有文献 > 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors.

3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors.

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.

journal_name

Mol Cancer Ther

journal_title

Molecular cancer therapeutics

authors

Onion D,Argent RH,Reece-Smith AM,Craze ML,Pineda RG,Clarke PA,Ratan HL,Parsons SL,Lobo DN,Duffy JP,Atherton JC,McKenzie AJ,Kumari R,King P,Hall BM,Grabowska AM

doi

10.1158/1535-7163.MCT-15-0598

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

753-63

issue

4

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-15-0598

journal_volume

15

pub_type

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