Evidence map›Paper›PMID 21494257›Full record

ReviewLeukemia2011

Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy.

L S Steelman, R A Franklin, S L Abrams, W Chappell, C R Kempf, J Bäsecke, F Stivala, M Donia, P Fagone, F Nicoletti and 6 more

Abstract readReview
PubMed Publisher
In one paragraph

Review in Leukemia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed
11.6field-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

138 citing papers in PubMed, 261 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014
    Trial
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024
    Review
  14. Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

78 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

16 authors at 5 institutions in 3 countries.

L S SteelmanDepartment of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA.
R A Franklin
S L Abrams
W Chappell
C R Kempf
J Bäsecke
F Stivala
M Donia
P Fagone
F Nicoletti
M Libra
P Ruvolo
V Ruvolo
C Evangelisti
A M Martelli
J A McCubrey
East Carolina University · USUniversity of Catania · ITThe University of Texas MD Anderson Cancer Center · USUniversity of Bologna · ITUniversity of Göttingen · DE

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

The Ras/Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway is often implicated in sensitivity and resistance to leukemia therapy. Dysregulated signaling through the Ras/Raf/MEK/ERK pathway is often the result of genetic alterations in critical components in this pathway as well as mutations at upstream growth factor receptors. Unrestricted leukemia proliferation and decreased sensitivity to apoptotic-inducing agents and chemoresistance are typically associated with activation of pro-survival pathways. Mutations in this pathway and upstream signaling molecules can alter sensitivity to small molecule inhibitors targeting components of this cascade as well as to inhibitors targeting other key pathways (for example, phosphatidylinositol 3 kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/Akt/mammalian target of rapamycin (mTOR)) activated in leukemia. Similarly, PI3K mutations can result in resistance to inhibitors targeting the Ras/Raf/MEK/ERK pathway, indicating important interaction points between the pathways (cross-talk). Furthermore, the Ras/Raf/MEK/ERK pathway can be activated by chemotherapeutic drugs commonly used in leukemia therapy. This review discusses the mechanisms by which abnormal expression of the Ras/Raf/MEK/ERK pathway can contribute to drug resistance as well as resistance to targeted leukemia therapy. Controlling the expression of this pathway could improve leukemia therapy and ameliorate human health.

Indexed as

Molecular Targeted TherapyAntineoplastic AgentsApoptosisCell DivisionDrug DesignDrug Resistance, NeoplasmExtracellular Signal-Regulated MAP KinasesGene Expression Regulation, LeukemicHumansLeukemiaMAP Kinase Signaling SystemMitogen-Activated Protein Kinase KinasesModels, BiologicalNeoplasm ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsAntineoplastic AgentsExtracellular Signal-Regulated MAP KinasesMitogen-Activated Protein Kinase KinasesNeoplasm ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase Inhibitorsraf Kinasesras Proteins

Identifiers

PMID21494257
OpenAlexW1596038553

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.