Evidence map›Paper›PMID 27476449›Full record

ArticleNature communications2016

Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.

Helena Escuin-Ordinas, Shuoran Li, Michael W Xie, Lu Sun, Willy Hugo, Rong Rong Huang, Jing Jiao, Felipe Meira de-Faria, Susan Realegeno, Paige Krystofinski and 12 more

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.4field-weighted citation impact, top 5% 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.

NCT07463365 phase1not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Phase 1, Open-Label Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy Study of Topically Administered LUT017 Gel for Cutaneous Wound Healing

TypeinterventionalSponsorAntoni RibasRan2026 to 2027Enrolled18ConditionsVenous Leg Ulcer, Chronic Non-Healing Cutaneous Wounds, VLUArmsLUT017 gel
NCT07463378 phase1not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Phase 1, Open-Label Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy Study of a Single Dose of Topically Administered LUT017 Gel for Cutaneous Wound Healing in Volunteers With Healthy Skin

TypeinterventionalSponsorAntoni RibasRan2026 to 2027Enrolled9ConditionsWound Healing, Acute Skin WoundsArmsLUT017,Topical BRAF inhibitor
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Targeting Signalling Pathways in Chronic Wound Healing.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
  15. TGF-β in developmental and fibrogenic EMTs.Seminars in cancer biology · 2022
    Review
  16. Transcriptome-Guided Drug Repurposing for Aggressive SCCs.International journal of molecular sciences · 2022
    Article
  17. Article
  18. Article
  19. Review
  20. 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

22 authors at 3 institutions in 2 countries.

Helena Escuin-OrdinasDivision of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA), 14-635 Factor Bldg, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
Shuoran LiDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles (UCLA), 7524 Boelter Hall, Los Angeles, California 90095, USA.
Michael W XieDivision of Experimental Radiation Oncology, Department of Radiation Oncology, University of California, Los Angeles (UCLA), B3-109 CHS, Los Angeles, California 90095, USA.
Lu SunDivision of Dermatology, Department of Medicine, University of California, Los Angeles (UCLA), 52-121 CHS and 13-942 Factor Bldg, Los Angeles, California 90095, USA.
Willy HugoDivision of Dermatology, Department of Medicine, University of California, Los Angeles (UCLA), 52-121 CHS and 13-942 Factor Bldg, Los Angeles, California 90095, USA.ORCID 0000-0002-1426-7190
Rong Rong HuangDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA), 924 Westwood Blvd. 730 and 1P-162 CHS, Los Angeles, California 90095, USA.
Jing JiaoDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles (UCLA), 329 Boyer Hall, Los Angeles, California 90095, USA.
Felipe Meira de-FariaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles (UCLA), 329 Boyer Hall, Los Angeles, California 90095, USA.ORCID 0000-0002-7875-0691
Susan RealegenoDepartment of Microbiology, Immunology &Molecular Genetics, University of California, Los Angeles (UCLA), 52-121 CHS, Los Angeles, California 90095, USA.
Paige KrystofinskiDivision of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA), 14-635 Factor Bldg, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
Ariel AzhdamDivision of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA), 14-635 Factor Bldg, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
Sara Marie D KomenanDivision of Surgical Oncology, Department of Surgery, 11-234 and 9-954 Factor Bldg, Los Angeles, California 90095, USA.
Mohammad AtefiDivision of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA), 14-635 Factor Bldg, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
Begoña Comin-AnduixDivision of Surgical Oncology, Department of Surgery, 11-234 and 9-954 Factor Bldg, Los Angeles, California 90095, USA.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles (UCLA), 3000C Terasaki Life Sciences Bldg, Los Angeles, California 90095, USA.
Alistair J CochranDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA), 924 Westwood Blvd. 730 and 1P-162 CHS, Los Angeles, California 90095, USA.
Robert L ModlinDivision of Dermatology, Department of Medicine, University of California, Los Angeles (UCLA), 52-121 CHS and 13-942 Factor Bldg, Los Angeles, California 90095, USA.
Harvey R HerschmanDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles (UCLA), 329 Boyer Hall, Los Angeles, California 90095, USA.
Roger S LoDivision of Dermatology, Department of Medicine, University of California, Los Angeles (UCLA), 52-121 CHS and 13-942 Factor Bldg, Los Angeles, California 90095, USA.
William H McBrideDivision of Experimental Radiation Oncology, Department of Radiation Oncology, University of California, Los Angeles (UCLA), B3-109 CHS, Los Angeles, California 90095, USA.
Tatiana SeguraDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles (UCLA), 7524 Boelter Hall, Los Angeles, California 90095, USA.
Antoni RibasDivision of Hematology/Oncology, Department of Medicine, University of California, Los Angeles (UCLA), 14-635 Factor Bldg, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
University of California, Los Angeles · USComprehensive Cardiovascular · USSociety of Surgical Oncology · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CUMBERLAND, WILLIAM GLEN · 1991 to 2018
$39.9M
Next Generation Cancer Immunotherapies to Defeat MelanomaR35CA197633 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTONI RIBAS · 2015 to 2026
$10.4M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DRY, SARAH M. · 2013 to 2017
$8.4M
NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA016042NCI NIH HHS R35 CA197633NIAID NIH HHS P30 AI028697
6 · The paper itself

Abstract

BRAF inhibitors are highly effective therapies for the treatment of BRAF(V600)-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds.

Indexed as

Administration, TopicalAnimalsCarcinogenesisCarcinogensCarcinoma, Squamous CellCell CycleCell Line, TumorFemaleHumansIncidenceIndolesKeratinocytesMAP Kinase Signaling SystemMiceMice, Inbred BALB CMitogen-Activated Protein Kinase KinasesBRAF protein, humanCarcinogensIndolesMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesSulfonamidestrametinibVemurafenib

Identifiers

PMID27476449
PMCPMC4974650
OpenAlexW2478221824

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.