Evidence map›Paper›PMID 28296140›Full record

ArticleMolecular oncology2017

Inhibitors of STAT3, β-catenin, and IGF-1R sensitize mouse PIK3CA-mutant breast cancer to PI3K inhibitors.

Vanessa F Merino, Soonweng Cho, Xiaohui Liang, Sunju Park, Kideok Jin, Qian Chen, Duojia Pan, Cynthia A Zahnow, Alan R Rein, Saraswati Sukumar

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-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

14 citing papers in PubMed, 22 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

10 authors at 3 institutions in 1 country.

Vanessa F MerinoDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Soonweng ChoDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Xiaohui LiangDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sunju ParkDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kideok JinDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qian ChenDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Duojia PanDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cynthia A ZahnowDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alan R ReinHIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD, USA.
Saraswati SukumarDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins University · USJohns Hopkins Medicine · USNational Cancer Institute · US

Funding

Search for XMRVZIABC011325 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI REIN, ALAN · 2010 to 2025
$6.2M
6 · The paper itself

Abstract

Although mutations in the phosphoinositide 3-kinase catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA-mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic mouse models expressing the human PIK3CA-H1047R- and the -E545K hotspot-mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cell lines derived from the PIK3CA tumors. Finally, public databases were analyzed to determine whether novel pathways identified in the mouse tumors were altered in human tumors harboring mutant PIK3CA. Mutant mice showed increased branching and delayed involution of the mammary gland compared to parental FVB/N mice. Mammary tumors arose in 30% of the MMTV-PIK3CA-H1047R and in 13% of -E545K mice. Compared to MMTV-Her-2 transgenic mouse mammary tumors, H1047R tumors showed increased upregulation of Wnt/β-catenin/Axin2, hepatocyte growth factor (Hgf)/Stat3, insulin-like growth factor 2 (Igf-2), and Igf-1R pathways. Inhibitors of STAT3, β-catenin, and IGF-1R sensitized H1047R-derived mouse tumor cells and PIK3CA-H1047R overexpressing human HS578T breast cancer cells to the cytotoxic effects of PI3K inhibitors. Analysis of The Cancer Genome Atlas database showed that, unlike primary PIK3CA-wild-type and HER-2

Indexed as

Phosphoinositide-3 Kinase InhibitorsAnimalsAntineoplastic Agentsbeta CateninCell Line, TumorClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleHumansMammary Neoplasms, ExperimentalMiceMice, TransgenicMutationProtein Kinase InhibitorsReceptor, IGF Type 1Antineoplastic Agentsbeta CateninClass I Phosphatidylinositol 3-KinasesErb-b2 Receptor Tyrosine KinasesIGF1R protein, humanPhosphoinositide-3 Kinase InhibitorsPIK3CA protein, humanProtein Kinase InhibitorsReceptor, IGF Type 1Receptors, SomatomedinRNA, MessengerSTAT3 protein, humanSTAT3 Transcription FactorbreastIGFmutationPIK3CASTAT3

Identifiers

PMID28296140
PMCPMC5527464
OpenAlexW2604877279

What Socratic 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 Socratic graph.