Evidence map›Paper›PMID 29743592›Full record

ArticleOncogene2018

A novel three-dimensional high-throughput screening approach identifies inducers of a mutant KRAS selective lethal phenotype.

Smitha Kota, Shurong Hou, William Guerrant, Franck Madoux, Scott Troutman, Virneliz Fernandez-Vega, Nina Alekseeva, Neeharika Madala, Louis Scampavia, Joseph Kissil and 1 more

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 32 citations in OpenAlex.

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  15. The Scripps Molecular Screening Center and Translational Research Institute.SLAS discovery : advancing life sciences R & D · 2019
    Article
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

11 authors at 1 institution in 1 country.

Smitha KotaDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Shurong HouDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
William GuerrantDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Franck MadouxDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Scott TroutmanDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Virneliz Fernandez-VegaDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Nina AlekseevaDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Neeharika MadalaDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Louis ScampaviaDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA.
Joseph KissilDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA. jkissil@scripps.edu.
Timothy P SpicerDepartment of Molecular Medicine, The Scripps Research Institute, Florida, USA. spicert@scripps.edu.
Scripps Research Institute · US

Funding

The Role of RAC1 in CancerR01CA124495 · NCI · WISTAR INSTITUTE · PI KISSIL, JOSEPH · 2009 to 2018
$3.9M
Advanced Development and Validation of 3 Dimensional Spheroid Culture of Primary Cancer Cells using Nano3D TechnologyR33CA206949 · NCI · SCRIPPS FLORIDA · PI SPICER, TIMOTHY PATRICK · 2016 to 2019
$1.6M
NCI NIH HHS R01 CA124495NCI NIH HHS R33 CA206949
6 · The paper itself

Abstract

The RAS proteins are the most frequently mutated oncogenes in cancer, with highest frequency found in pancreatic, lung, and colon tumors. Moreover, the activity of RAS is required for the proliferation and/or survival of these tumor cells and thus represents a high-value target for therapeutic development. Direct targeting of RAS has proven challenging for multiple reasons stemming from the biology of the protein, the complexity of downstream effector pathways and upstream regulatory networks. Thus, significant efforts have been directed at identifying downstream targets on which RAS is dependent. These efforts have proven challenging, in part due to confounding factors such as reliance on two-dimensional adherent monolayer cell cultures that inadequately recapitulate the physiologic context to which cells are exposed in vivo. To overcome these issues, we implemented a high-throughput screening (HTS) approach using a spheroid-based 3-dimensional culture format, thought to more closely reflect conditions experienced by cells in vivo. Using isogenic cell pairs, differing in the status of KRAS, we identified Proscillaridin A as a selective inhibitor of cells harboring the oncogenic KRas

Indexed as

Antineoplastic AgentsCell Culture TechniquesCell Line, TumorDrug Screening Assays, AntitumorHumansMutationPhenotypeProscillaridinProto-Oncogene Proteins p21(ras)Signal TransductionAntineoplastic AgentsKRAS protein, humanProscillaridinProto-Oncogene Proteins p21(ras)

Identifiers

PMID29743592
PMCPMC6138545
OpenAlexW2802334782

What OpenQuestion holds

Textmetadata
LicenceTDM
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.