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

BMC Medicine
Sara CharmsazLeonie S Young

Abstract

Metastatic 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. Global 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. Bioinformatic 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 ta...Continue Reading

Associated Clinical Trials

References

May 11, 2005·Biochemical and Biophysical Research Communications·Pengcheng ZhuShouyuan Zhao
Mar 7, 2006·Journal of Cellular Physiology·Nadia GabelliniG Palù
May 26, 2006·Nature Reviews. Cancer·Patrick Mehlen, Alain Puisieux
May 13, 2008·Journal of Mammary Gland Biology and Neoplasia·Mark D Sternlicht, Susan W Sunnarborg
Sep 3, 2008·Molecular Aspects of Medicine·Dylan R EdwardsCaroline J Pennington
Nov 14, 2008·Nature Reviews. Cancer·Gillian Murphy
Dec 4, 2008·Seminars in Cell & Developmental Biology·Karina Reiss, Paul Saftig
May 8, 2009·Nature·Paula D BosJoan Massagué
Jul 30, 2009·British Journal of Biomedical Science·S L TurnerR A D Bunning
Jan 30, 2010·International Journal of Cell Biology·Nadia Gabellini, Valentina Masola
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yuko FukataMasaki Fukata
Sep 13, 2011·Clinical Proteomics·Michael J DuffyPatricia M McGowan
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Jun 6, 2012·Journal of Mammary Gland Biology and Neoplasia·Frances L ShawRobert B Clarke
Feb 5, 2014·Molecular Cancer Therapeutics·Maija HyvönenPirjo Laakkonen
Dec 3, 2014·Drug Discovery Today·Keld Fosgerau, Torsten Hoffmann
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Feb 12, 2015·Cancer Cell·David P KodackRakesh K Jain
Mar 1, 2015·Molecular Cancer Therapeutics·Deepak KanojiaAtique U Ahmed
Mar 1, 2015·The AAPS Journal·Gadi G Bornstein
Jul 15, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Alexandra NabaRichard O Hynes
Aug 5, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jean McBryanLeonie S Young
Aug 16, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Siker KimbungUNKNOWN TEX study group
Jan 15, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Damir VareslijaLeonie Young
May 22, 2016·Bioinformatics·Zuguang GuMatthias Schlesner
Oct 1, 2016·Journal of Cancer Research and Clinical Oncology·Yijun HuShanrong Liu
Mar 7, 2017·Nature Methods·Rob PatroCarl Kingsford
Mar 23, 2017·Journal of Biomedical Science·Susan MarqusTerrence J Piva
Apr 13, 2017·BMC Medicine·Sara CharmsazLeonie S Young
Nov 21, 2017·Nucleic Acids Research·Kelsy C CottoMalachi Griffith
Mar 24, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elspeth WardLeonie S Young
Jun 10, 2018·Matrix Biology : Journal of the International Society for Matrix Biology·Timothy J Mead, Suneel S Apte
Jul 3, 2018·Journal of the National Cancer Institute·Damir VarešlijaLeonie S Young
Oct 3, 2018·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Jun LiShidai Jin
Dec 12, 2018·Journal of Colloid and Interface Science·Attilio MarinoGianni Ciofani
Jan 13, 2019·Clinical Science·Catharina ConradJörg W Bartsch

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Citations

May 22, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachel BleachMarie McIlroy

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Methods Mentioned

BETA
RNA-seq
RNAseq
RNA seq
protein array
xenograft
PCR
Genotyping
FACS
Transmission electron microscopy

Clinical Trials Mentioned

NCT01840293

Software Mentioned

ClueGo
DESeq2
ComplexHeatmap
Salmon
GraphPad
EnhancedVolcano
Matrisome
DOCK
Prism
CompareCluster

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