Evidence map›Paper›PMID 27081080›Full record

ArticleOncotarget2016

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer.

Bhaskar Bhattacharya, Sarah Hong Hui Low, Mei Ling Chong, Dilys Chia, King Xin Koh, Nur Sabrina Sapari, Stanley Kaye, Huynh Hung, Touati Benoukraf, Richie Soong

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

10 authors.

Bhaskar BhattacharyaCancer Science Institute of Singapore, National University of Singapore, Singapore.
Sarah Hong Hui LowCancer Science Institute of Singapore, National University of Singapore, Singapore.
Mei Ling ChongCancer Science Institute of Singapore, National University of Singapore, Singapore.
Dilys ChiaDepartment of Pharmacy, National University of Singapore, Singapore.
King Xin KohDepartment of Pathology, National University of Singapore, Singapore.
Nur Sabrina SapariCancer Science Institute of Singapore, National University of Singapore, Singapore.
Stanley KayeDrug Development Unit, Royal Marsden NHS Trust, The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Huynh HungLaboratory of Molecular Endocrinology, National Cancer Centre of Singapore, Singapore.
Touati BenoukrafCancer Science Institute of Singapore, National University of Singapore, Singapore.
Richie SoongCancer Science Institute of Singapore, National University of Singapore, Singapore.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Historically, understanding of acquired resistance (AQR) to combination treatment has been based on knowledge of resistance to its component agents. To test whether an altered drug interaction could be an additional factor in AQR to combination treatment, models of AQR to combination and single agent MEK and PI3K inhibitor treatment were generated. Combination indices indicated combination treatment of PI3K and MEK inhibitors remained synergistic in cells with AQR to single agent but not combination AQR cells. Differences were also observed between the models in cellular phenotypes, pathway signaling and drug cross-resistance. Genomics implicated TGFB2-EDN1 overexpression as candidate determinants in models of AQR to combination treatment. Supplementation of endothelin in parental cells converted synergism to antagonism. Silencing of TGFB2 or EDN1 in cells with AQR conferred synergy between PI3K and MEK inhibitor. These results highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction.

Indexed as

Phosphoinositide-3 Kinase InhibitorsAnimalsAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug Resistance, NeoplasmDrug SynergismHCT116 CellsHumansMAP Kinase Kinase KinasesMiceMice, SCIDProtein Kinase InhibitorsXenograft Model Antitumor AssaysMAP Kinase Kinase KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase Inhibitorsacquired resistancecombination therapyMEK inhibitorsPI3K inhibitorssynergy

Identifiers

PMID27081080
PMCPMC5045388

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.