Evidence map›Paper›PMID 25247711›Full record

ArticlePloS one2014

3-Dimensional culture systems for anti-cancer compound profiling and high-throughput screening reveal increases in EGFR inhibitor-mediated cytotoxicity compared to monolayer culture systems.

Amy L Howes, Robyn D Richardson, Darren Finlay, Kristiina Vuori

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 119 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Amy L HowesCancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
Robyn D RichardsonCancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
Darren FinlayCancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
Kristiina VuoriCancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
Sanford Burnham Prebys Medical Discovery Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
High throughput screening in human 3D spheroids of epithelial, endothelial, and sRC1EB011780 · NIBIB · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI VUORI, KRISTIINA · 2009 to 2010
$955k
NCI NIH HHS P30 CA030199NIBIB NIH HHS 1 RC1 EB011780-01NIBIB NIH HHS RC1 EB011780
6 · The paper itself

Abstract

3-dimensional (3D) culture models have the potential to bridge the gap between monolayer cell culture and in vivo studies. To benefit anti-cancer drug discovery from 3D models, new techniques are needed that enable their use in high-throughput (HT) screening amenable formats. We have established miniaturized 3D culture methods robust enough for automated HT screens. We have applied these methods to evaluate the sensitivity of normal and tumorigenic breast epithelial cell lines against a panel of oncology drugs when cultured as monolayers (2D) and spheroids (3D). We have identified two classes of compounds that exhibit preferential cytotoxicity against cancer cells over normal cells when cultured as 3D spheroids: microtubule-targeting agents and epidermal growth factor receptor (EGFR) inhibitors. Further improving upon our 3D model, superior differentiation of EC50 values in the proof-of-concept screens was obtained by co-culturing the breast cancer cells with normal human fibroblasts and endothelial cells. Further, the selective sensitivity of the cancer cells towards chemotherapeutics was observed in 3D co-culture conditions, rather than as 2D co-culture monolayers, highlighting the importance of 3D cultures. Finally, we examined the putative mechanisms that drive the differing potency displayed by EGFR inhibitors. In summary, our studies establish robust 3D culture models of human cells for HT assessment of tumor cell-selective agents. This methodology is anticipated to provide a useful tool for the study of biological differences within 2D and 3D culture conditions in HT format, and an important platform for novel anti-cancer drug discovery.

Indexed as

High-Throughput Screening AssaysAntineoplastic AgentsBreastBreast NeoplasmsCell Culture TechniquesCell Line, TumorCells, CulturedCoculture TechniquesDose-Response Relationship, DrugDrug Screening Assays, AntitumorEpithelial CellsErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleFibroblastsHumansAntineoplastic AgentsEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsNeoplasm ProteinsProtein Kinase InhibitorsTubulin Modulators

Identifiers

PMID25247711
PMCPMC4172726
OpenAlexW2049682885

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.