Evidence map›Paper›PMID 26640591›Full record

ArticleJournal of Cancer2015

Comprehensive Two- and Three-Dimensional RNAi Screening Identifies PI3K Inhibition as a Complement to MEK Inhibitor AS703026 for Combination Treatment of Triple-Negative Breast Cancer.

Jangsoon Lee, Rachael Galloway, Geoff Grandjean, Justin Jacob, Juliane Humphries, Chandra Bartholomeusz, Samantha Goodstal, Bora Lim, Geoffrey Bartholomeusz, Naoto T Ueno and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 21 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

11 authors at 2 institutions in 1 country.

Jangsoon Lee1. Section of Translational Breast Cancer Research and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology - Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Rachael Galloway2. Department of Bioinformatics and Computational Biology - Unit 1410, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Geoff Grandjean3. Department of Experimental Therapeutics - Unit 1950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Justin Jacob3. Department of Experimental Therapeutics - Unit 1950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Juliane Humphries1. Section of Translational Breast Cancer Research and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology - Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Chandra Bartholomeusz1. Section of Translational Breast Cancer Research and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology - Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Samantha Goodstal4. EMD Serono Research & Development Institute, Inc., 45A Middlesex Turnpike, Billerica, MA, 01821, USA.
Bora Lim1. Section of Translational Breast Cancer Research and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology - Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Geoffrey Bartholomeusz3. Department of Experimental Therapeutics - Unit 1950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Naoto T Ueno1. Section of Translational Breast Cancer Research and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, Department of Breast Medical Oncology - Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
Arvind Rao2. Department of Bioinformatics and Computational Biology - Unit 1410, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA;
The University of Texas MD Anderson Cancer Center · USBreast Cancer Research Foundation · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Markers of sensivity to the EGFR inhibitor erlotinib in breast cancerR01CA123318 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI UENO, NAOTO T. · 2007 to 2012
$1.4M
Development of Targeted Therapy for ERK Pathway in Breast CancerR00CA139006 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BARTHOLOMEUSZ, CHANDRA · 2013 to 2015
$725k
NCI NIH HHS P30 CA016672NCI NIH HHS R00 CA139006NCI NIH HHS R01 CA123318
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is a major cause of death among breast cancer patients that results from intrinsic and acquired resistance to systemic chemotherapies. To identify novel targets for effective treatment of TNBC through combination strategies with MEK inhibitor (AS703026), we used a novel method of combining high-throughput two- and three-dimensional (2D and 3D) RNAi screening. TNBC cells were transfected with a kinome siRNA library comprising siRNA targeting 790 kinases under both 2D and 3D culture conditions with or without AS703026. Molecule activity predictor analysis revealed the PI3K pathway as the major target pathway in our RNAi combination studies in TNBC. We found that PI3K inhibitor SAR245409 (also called XL765) combined with AS703026 synergistically inhibited proliferation compared with either drug alone (P < 0.001). Reduced in vitro colony formation (P < 0.001) and migration and invasion ability were also observed with the combination treatment (P<0.01). Our data suggest that SAR245409 combined with AS703026 may be effective in patients with TNBC. We conclude that a novel powerful high-throughput RNAi assays were able to identify anti-cancer drugs as single or combinational agents. Integrated and multi-system RNAi screening methods can complement difference between in vitro and in vivo culture conditions, and enriches targets that are close to the in vivo condition.

Indexed as

AS703026multicellular tumor spheroidprojection formation.SAR245409three-dimensional RNAi screeningTriple-negative breast cancertwo-dimensional RNAi screening

Identifiers

PMID26640591
PMCPMC4643087
OpenAlexW2193888432

What OpenQuestion holds

Textmetadata
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.