Evidence map›Paper›PMID 33139506›Full record

ReviewMolecular cancer research : MCR2021

The MEK/ERK Network as a Therapeutic Target in Human Cancer.

Renee Barbosa, Lucila A Acevedo, Ronen Marmorstein

Open access · bronzeAbstract readReview
In one paragraph

Review in Molecular cancer research : MCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

118 citing papers in PubMed, 1 synthesis or guideline pooled it, 208 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Tumor-Associated Macrophage Exosomal miR-142-5p Drives Prostate Cancer Neuroendocrine Differentiation via RERG/Ras/ERK Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Therapeutic Effects ofInternational journal of molecular sciences · 2026
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

58 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

3 authors at 2 institutions in 1 country.

Renee BarbosaSchool of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID https://orcid.org/0000-0003-0126-9610
Lucila A AcevedoDepartment of Biochemistry & Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID https://orcid.org/0000-0001-7234-3676
Ronen MarmorsteinDepartment of Biochemistry & Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. marmor@upenn.edu.ORCID https://orcid.org/0000-0003-4373-4752
Cancer Research Institute · USUniversity of the Arts · US

Funding

Development of BRAF Dimer Inhibitors to Treat Drug Resistant MelanomaR01CA226888 · NCI · UNIVERSITY OF PENNSYLVANIA · PI MARMORSTEIN, RONEN, WINKLER, JEFFREY D · 2019 to 2023
$3.4M
NCI NIH HHS R01 CA226888
6 · The paper itself

Abstract

The RAS-RAF-MEK-ERK pathway is the most well-studied of the MAPK cascades and is critical for cell proliferation, differentiation, and survival. Abnormalities in regulation resulting from mutations in components of this pathway, particularly in upstream proteins, RAS and RAF, are responsible for a significant fraction of human cancers and nearly all cutaneous melanomas. Activation of receptor tyrosine kinases by growth factors and various extracellular signals leads to the sequential activation of RAS, RAF, MEK, and finally ERK, which activates numerous transcription factors and facilitates oncogenesis in the case of aberrant pathway activation. While extensive studies have worked to elucidate the activation mechanisms and structural components of upstream MAPK components, comparatively less attention has been directed toward the kinases, MEK and ERK, due to the infrequency of oncogenic-activating mutations in these kinases. However, acquired drug resistance has become a major issue in the treatment of RAS- and RAF-mutated cancers. Targeting the terminal kinases in the MAPK cascade has shown promise for overcoming many of these resistance mechanisms and improving treatment options for patients with MAPK-aberrant cancers. Here, we will describe the role of MEK and ERK in MAPK signaling and summarize the current understanding of their interaction and activation mechanisms. We will also discuss existing approaches for targeting MEK and ERK, and the benefits of alternative strategies. Areas requiring further exploration will be highlighted to guide future research endeavors and aid in the development of alternative therapeutic strategies to combat surmounting drug resistance in treating MAPK-mediated cancers. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/3/361/F1.large.jpg.

Indexed as

HumansMAP Kinase Signaling SystemMolecular Targeted TherapyNeoplasms

Identifiers

PMID33139506
PMCPMC7925338
OpenAlexW3094801273

What OpenQuestion holds

Textmetadata
LicenceTDM
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.