Evidence map›Paper›PMID 40615399›Full record

ArticleNature communications2025

Cx43 enhances response to BRAF/MEK inhibitors by reducing DNA repair capacity.

Adrián Varela-Vázquez, Amanda Guitián-Caamaño, Paula Carpintero-Fernández, Alexander Carneiro-Figueira, Vanesa Álvarez, Marta Varela-Eirín, Teresa Calleja-Chuclá, Susana B Bravo-López, Anxo Vidal, Juan Sendón-Lago and 15 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Beyond the gap: moonlighting functions of connexins in cancer.Cell communication and signaling : CCS · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Potential Anticancer Effect ofInternational journal of molecular sciences · 2025
    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

25 authors.

Adrián Varela-Vázquez *CELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain.
Amanda Guitián-Caamaño *CELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain.
Paula Carpintero-Fernández *CELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain.
Alexander Carneiro-Figueira *CELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain.
Vanesa ÁlvarezDivision of Molecular, Cell, and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
Marta Varela-EirínCELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain.
Teresa Calleja-ChucláPharmacy Service CHUAC. Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain.
Susana B Bravo-LópezProteomics Laboratory, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.ORCID http://orcid.org/0000-0001-7615-3079
Anxo VidalCiCLOn, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), E15782, Santiago de Compostela, Spain.ORCID http://orcid.org/0000-0002-0866-4202
Juan Sendón-LagoDepartment of Physiology-Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.ORCID http://orcid.org/0000-0001-8360-0033
Marina Rodriguez-Candela MateosInstituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain.
José R CaeiroDepartment of Orthopaedic Surgery and Traumatology, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
Victoria Sanz-MorenoThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-5096-9456
Trond AasenTranslational Molecular Pathology, Vall d'Hebron Institute of Research (VHIR), Autonomous University of Barcelona, CIBERONC, Barcelona, Spain.ORCID http://orcid.org/0000-0003-0763-2695
Miguel G BlancoDepartment of Biochemistry and Molecular Biology, CIMUS, Universidade de Santiago de Compostela-Instituto de Investigación Sanitaria (IDIS), Santiago de Compostela, Spain.ORCID http://orcid.org/0000-0002-2883-7326
Guadalupe SabioUniversidade de Santiago de Compostela-Instituto de Investigación Sanitaria (IDIS), Madrid, Spain.ORCID http://orcid.org/0000-0002-2822-0625
María QuindósMedical Oncology Service. Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain.
Carmen RivasCentro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Instituto de Investigaciones Sanitarias (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.ORCID http://orcid.org/0000-0002-0518-7199
David SantamaríaCentro de Investigación del Cáncer, CSIC. University of Salamanca, Salamanca, Spain.ORCID http://orcid.org/0000-0002-4711-3569
Carlos Fernandez-LozanoCITIC-Research Center of Information and Communication Technologies. Department of Computer Science and Information Technologies, Faculty of Computer Science, Universidade da Coruna, A Coruña, 15071, Spain.ORCID http://orcid.org/0000-0003-0413-5677
Eduardo FonsecaCELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain.
Pablo HuertasCentro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas-Universidad Pablo de Olavide, Sevilla, Spain.ORCID http://orcid.org/0000-0002-1756-4449
Berta Sánchez-LaordenInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, San Juan de Alicante, Spain.ORCID http://orcid.org/0000-0002-6499-6332
Constance AlabertDivision of Molecular, Cell, and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK.
María D MayánCELLCOM Research Group. Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo (Before: Instituto de Investigación Biomédica de A Coruña (INIBIC), Servizo Galego de Saúde (SERGAS), Universidade da Coruña (UDC), A Coruña, Spain), Pontevedra, Spain. mariadolores.mayan@uvigo.gal.ORCID http://orcid.org/0000-0002-5809-9440

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BRAF and MEK inhibitors (BRAF/MEKi) have radically changed the treatment landscape of advanced BRAF mutation-positive tumours. However, limited efficacy and emergence of drug resistance are major barriers for successful treatments. Here, by using relevant preclinical models, we find that Connexin43 (Cx43), a protein that plays a role in cell-to-cell communication, enhances the effectiveness of BRAF/MEKi by recruiting DNA repair complexes to lamin-associated domains and promoting persistent DNA damage and cellular senescence. The nuclear compartmentalization promoted by Cx43 contributes to genome instability and synthetic lethality caused by excessive DNA damage, which could provide a therapeutic approach for these tumours to overcome drug resistance. Based on these findings, we designed a drug combination using small extracellular vesicles (sEVs) to deliver the full-Cx43 in combination with the BRAF/MEKi. This study reveals Cx43 as a regulator of DNA repair and BRAF/MEKi response, highlighting the therapeutic potential that this approach could eventually have in the clinic to overcome the limitations of current therapies and improve treatment outcomes for patients with advanced BRAF mutant tumours.

Indexed as

Connexin 43DNA RepairProtein Kinase InhibitorsProto-Oncogene Proteins B-rafAnimalsCell Line, TumorCellular SenescenceDNA DamageDrug Resistance, NeoplasmExtracellular VesiclesHumansMiceMutationBRAF protein, humanConnexin 43GJA1 protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins B-raf

Identifiers

PMID40615399
PMCPMC12227752

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.