Evidence map›Paper›PMID 26399658›Full record

ReviewNature reviews. Cancer2015

MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road.

Christopher J Caunt, Matthew J Sale, Paul D Smith, Simon J Cook

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 373 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
373citing papers in PubMed, 1 pooled it
25.9field-weighted citation impact, top 1% 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

373 citing papers in PubMed, 1 synthesis or guideline pooled it, 604 citations in OpenAlex.

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  4. Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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313 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Christopher J CauntDepartment of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Matthew J SaleSignalling Laboratory, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Paul D SmithAstraZeneca, Oncology iMed, Cancer Biosciences, Cancer Research UK, Li Ka Shing Centre, Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.
Simon J CookSignalling Laboratory, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Babraham Institute · GBUniversity of Bath · GB

Funding

Biotechnology and Biological Sciences Research Council BBS/E/B/0000C199Biotechnology and Biological Sciences Research Council BBS/E/B/0000H151Biotechnology and Biological Sciences Research Council BBS/E/B/0000H248Biotechnology and Biological Sciences Research Council BBS/E/B/000C0417Biotechnology and Biological Sciences Research Council BBS/E/B/000C0419Cancer Research UK 14867
6 · The paper itself

Abstract

The role of the ERK signalling pathway in cancer is thought to be most prominent in tumours in which mutations in the receptor tyrosine kinases RAS, BRAF, CRAF, MEK1 or MEK2 drive growth factor-independent ERK1 and ERK2 activation and thence inappropriate cell proliferation and survival. New drugs that inhibit RAF or MEK1 and MEK2 have recently been approved or are currently undergoing late-stage clinical evaluation. In this Review, we consider the ERK pathway, focusing particularly on the role of MEK1 and MEK2, the 'gatekeepers' of ERK1/2 activity. We discuss their validation as drug targets, the merits of targeting MEK1 and MEK2 versus BRAF and the mechanisms of action of different inhibitors of MEK1 and MEK2. We also consider how some of the systems-level properties (intrapathway regulatory loops and wider signalling network connections) of the ERK pathway present a challenge for the success of MEK1 and MEK2 inhibitors, discuss mechanisms of resistance to these inhibitors, and review their clinical progress.

Indexed as

HumansMAP Kinase Kinase 1MAP Kinase Kinase 2MAP Kinase Signaling SystemNeoplasmsProtein Kinase InhibitorsSignal TransductionMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2Protein Kinase Inhibitors

Identifiers

PMID26399658
OpenAlexW1848470479

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.