Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 04 2023
26 04 2023
Historique:
received:
18
05
2020
accepted:
22
02
2023
medline:
28
4
2023
pubmed:
27
4
2023
entrez:
26
4
2023
Statut:
epublish
Résumé
Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility.
Identifiants
pubmed: 37100807
doi: 10.1038/s41467-023-36910-5
pii: 10.1038/s41467-023-36910-5
pmc: PMC10133315
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Bevacizumab
2S9ZZM9Q9V
Antibodies, Monoclonal
0
Angiogenesis Inhibitors
0
CD5L protein, human
0
Apoptosis Regulatory Proteins
0
Receptors, Scavenger
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2407Subventions
Organisme : NCI NIH HHS
ID : T32 CA101642
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA209904
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217685
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA221675
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY028102
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Drug Resist Updat. 2008 Dec;11(6):219-30
pubmed: 18948057
Mol Ther. 2018 Oct 3;26(10):2487-2495
pubmed: 30131301
Methods Enzymol. 1996;267:275-301
pubmed: 8743323
Cell Metab. 2010 Jun 9;11(6):479-92
pubmed: 20519120
Sci Signal. 2009 May 26;2(72):re3
pubmed: 19471024
PLoS One. 2015 Jul 29;10(7):e0134403
pubmed: 26221730
Cell Rep. 2014 Oct 9;9(1):61-74
pubmed: 25284781
Clin Cancer Res. 2017 Nov 15;23(22):7034-7046
pubmed: 28855350
Am J Pathol. 2003 Mar;162(3):837-47
pubmed: 12598318
J Leukoc Biol. 2015 Aug;98(2):173-84
pubmed: 26048980
Neurology. 2008 Mar 4;70(10):779-87
pubmed: 18316689
J Exp Med. 1999 Jan 18;189(2):413-22
pubmed: 9892623
J Clin Invest. 2018 Oct 1;128(10):4329-4342
pubmed: 30047927
Oncogene. 2004 Oct 21;23(49):8065-77
pubmed: 15361855
Am J Obstet Gynecol. 2005 Mar;192(3):819-25
pubmed: 15746677
Nat Med. 2011 Nov 07;17(11):1359-70
pubmed: 22064426
Nat Rev Cancer. 2008 Aug;8(8):592-603
pubmed: 18650835
Am J Physiol Lung Cell Mol Physiol. 2009 Dec;297(6):L1082-90
pubmed: 19801450
Methods. 2016 Mar 15;97:58-68
pubmed: 26542762
JCI Insight. 2019 Mar 21;5:
pubmed: 30896449
Cancer Cell. 2013 Aug 12;24(2):229-41
pubmed: 23871637
J Immunol. 2009 Feb 1;182(3):1648-59
pubmed: 19155514
EMBO Mol Med. 2020 Jun 8;12(6):e11217
pubmed: 32400970
Cancer Cell. 2005 Oct;8(4):299-309
pubmed: 16226705
Clin Cancer Res. 2008 Oct 15;14(20):6371-5
pubmed: 18927275
N Engl J Med. 1971 Nov 18;285(21):1182-6
pubmed: 4938153
PLoS One. 2022 Dec 16;17(12):e0277956
pubmed: 36525420
J Neurosurg. 2009 Jan;110(1):173-80
pubmed: 18834263
N Engl J Med. 2008 May 8;358(19):2039-49
pubmed: 18463380