Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis.
Clin Cancer Res
; 23(11): 2806-2816, 2017 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-27923843
ABSTRACT
Purpose:
AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple-negative breast cancer (TNBC).ExperimentalDesign:
We evaluate the antitumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration, and invasion signaling pathways.Results:
Treatment with 20G7-D9 inhibited tumor growth and bone metastasis formation in AXL-positive TNBC cell xenografts or PDX, but not in AXL-negative PDX, highlighting AXL role in cancer growth and invasion. In vitro stimulation of AXL-positive cancer cells by its ligand GAS6 induced the expression of several EMT-associated genes (SNAIL, SLUG, and VIM) through an intracellular signaling implicating the transcription factor FRA-1, important in cell invasion and plasticity, and increased their migration/invasion capacity. 20G7-D9 induced AXL degradation and inhibited all AXL/GAS6-dependent cell signaling implicated in EMT and in cell migration/invasion.Conclusions:
The anti-AXL antibody 20G7-D9 represents a promising therapeutic strategy in TNBC with mesenchymal features by inhibiting AXL-dependent EMT, tumor growth, and metastasis formation. Clin Cancer Res; 23(11); 2806-16. ©2016 AACR.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Anti-Idiotypic
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Proto-Oncogene Proteins
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Receptor Protein-Tyrosine Kinases
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Cell Proliferation
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Triple Negative Breast Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2017
Document type:
Article
Affiliation country:
France