Evidence map›Paper›PMID 33208158›Full record

ArticleBMC medicine2020

ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis.

Sara Charmsaz, Ben Doherty, Sinéad Cocchiglia, Damir Varešlija, Attilio Marino, Nicola Cosgrove, Ricardo Marques, Nolan Priedigkeit, Siobhan Purcell, Fiona Bane and 17 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in BMC medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
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  5. Review
  6. TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  13. Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 6 institutions in 3 countries.

Sara CharmsazEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Ben DohertyEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Sinéad CocchigliaEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Damir VarešlijaEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Attilio MarinoSmart Bio-Interfaces, Istituto Italiano di Tecnologia, Scuola Superiore Sant'Anna, Pontedera, Italy.
Nicola CosgroveEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Ricardo MarquesEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Nolan PriedigkeitWomen's Cancer Research Centre, Magee-Women's Research Institute, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Siobhan PurcellEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Fiona BaneEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Jarlath BolgerEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Christopher ByrneEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Philip J O'HalloranDepartment of Neurosurgery, National Neurosurgical Centre, Beaumont Hospital, Dublin, Ireland.
Francesca BrettDepartment of Neuropathology, Beaumont Hospital, Dublin, Ireland.
Katherine SheehanDepartment of Pathology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Kieran BrennanDepartment of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.
Ann M HopkinsDepartment of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.
Stephen KeelanEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Petra JagustEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Stephen MaddenData Science Centre, Royal College of Surgeons in Ireland, Dublin, Ireland.
Chiara MartinelliSmart Bio-Interfaces, Istituto Italiano di Tecnologia, Scuola Superiore Sant'Anna, Pontedera, Italy.
Matteo BattagliniSmart Bio-Interfaces, Istituto Italiano di Tecnologia, Scuola Superiore Sant'Anna, Pontedera, Italy.
Steffi OesterreichWomen's Cancer Research Centre, Magee-Women's Research Institute, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Adrian V LeeWomen's Cancer Research Centre, Magee-Women's Research Institute, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Gianni CiofaniSmart Bio-Interfaces, Istituto Italiano di Tecnologia, Scuola Superiore Sant'Anna, Pontedera, Italy.
Arnold D K HillDepartment of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.
Leonie S YoungEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland. lyoung@rcsi.ie.
Royal College of Surgeons in Ireland · IEBeaumont Hospital · IEItalian Institute of Technology · ITMagee-Womens Research Institute · USScuola Superiore Sant'Anna · ITUPMC Hillman Cancer Center · US

Funding

Breast Cancer Now 2018JulPR1094Breast Cancer Now 2019AugSF1310EU-FP7 EU-FP7-IAPPIrish Cancer Society CCRC13GALScience Foundation Ireland 12/1A/1294Science Foundation Ireland 15/BIAP/3185
6 · The paper itself

Abstract

backgroundMetastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood-brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets.

methodsGlobal transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target's natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis.

resultsBioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis.

conclusionADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.

Indexed as

ADAM ProteinsAnimalsBiomimetic MaterialsBrain NeoplasmsBreast NeoplasmsFemaleGene Expression ProfilingHumansIntracellular Signaling Peptides and ProteinsMolecular Targeted TherapyNeoplasm Recurrence, LocalNerve Tissue ProteinsPeptidesADAM22 protein, humanADAM ProteinsIntracellular Signaling Peptides and ProteinsLGI1 protein, humanNerve Tissue ProteinsPeptidesADAM22Blood–brain barrierBrain metastasesBreast cancer metastasesECM signallingLGI1Targeted therapy

Identifiers

PMID33208158
PMCPMC7677775
OpenAlexW3104389503

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.