Expression of MT4-MMP, EGFR, and RB in Triple-Negative Breast Cancer Strongly Sensitizes Tumors to Erlotinib and Palbociclib Combination Therapy.
Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Biomarkers, Tumor
/ analysis
COS Cells
Cell Line, Tumor
Chlorocebus aethiops
Drug Resistance, Neoplasm
/ genetics
ErbB Receptors
/ analysis
Erlotinib Hydrochloride
/ pharmacology
Feasibility Studies
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Matrix Metalloproteinases, Membrane-Associated
/ analysis
Mice
Middle Aged
Piperazines
/ pharmacology
Prognosis
Pyridines
/ pharmacology
Retinoblastoma Binding Proteins
/ analysis
Triple Negative Breast Neoplasms
/ drug therapy
Ubiquitin-Protein Ligases
/ analysis
Xenograft Model Antitumor Assays
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
13
06
2018
revised:
15
10
2018
accepted:
27
11
2018
pubmed:
7
12
2018
medline:
28
5
2020
entrez:
4
12
2018
Statut:
ppublish
Résumé
Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), and retinoblastoma protein (RB). EGFR and MT4-MMP were coexpressed in >70% of TNBC samples and PDX-TNBC, among which approximately 60% maintained RB expression. Notably, approximately 50% of all TNBC and PDX-TNBC expressed the three biomarkers. Single erlotinib and palbociclib treatments drastically reduced the We defined a new association of three biomarkers (MT4-MMP/EGFR/RB) expressed together in 50% of TNBC and demonstrated its usefulness to predict the TNBC response to anti-EGFR and anti-CDK4/6 drugs used in single or combined therapy.
Identifiants
pubmed: 30504427
pii: 1078-0432.CCR-18-1880
doi: 10.1158/1078-0432.CCR-18-1880
doi:
Substances chimiques
Biomarkers, Tumor
0
Piperazines
0
Pyridines
0
RB1 protein, human
0
Retinoblastoma Binding Proteins
0
Erlotinib Hydrochloride
DA87705X9K
Ubiquitin-Protein Ligases
EC 2.3.2.27
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
MMP17 protein, human
EC 3.4.24.-
Matrix Metalloproteinases, Membrane-Associated
EC 3.4.24.-
palbociclib
G9ZF61LE7G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1838-1850Informations de copyright
©2018 American Association for Cancer Research.