Evidence map›Paper›PMID 27465249›Full record

ArticleBMC cancer2016

PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma.

R L Ross, H R McPherson, L Kettlewell, S D Shnyder, C D Hurst, O Alder, M A Knowles

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

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  16. Silencing theYonsei medical journal · 2019
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  19. The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    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

7 authors at 2 institutions in 1 country.

R L RossSection of Experimental Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
H R McPhersonSection of Experimental Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
L KettlewellSection of Experimental Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
S D ShnyderInstitute of Cancer Therapeutics, University of Bradford, Richmond Road, Bradford, BD7 1DP, UK.
C D HurstSection of Experimental Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
O AlderSection of Experimental Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
M A KnowlesSection of Experimental Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK. m.a.knowles@leeds.ac.uk.
St James's University Hospital · GBUniversity of Bradford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMany urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases.

methodsWe used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway.

resultsSpecific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance.

conclusionsMutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer.

Indexed as

AnimalsBlotting, WesternCarcinoma, Transitional CellCell Line, TumorCell MovementCell ProliferationCell Transformation, NeoplasticClass I Phosphatidylinositol 3-KinasesGene Knockdown TechniquesHeterograftsHumansImmunohistochemistryMaleMiceMice, Inbred BALB CMutationClass I Phosphatidylinositol 3-KinasesPIK3CA protein, humanBladder cancerPI3K signalingPIK3CAUrothelium

Identifiers

PMID27465249
PMCPMC4964013
OpenAlexW2479754916

What OpenQuestion holds

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LicenceCC BY
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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.