Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy.
Adult
Aged
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Chemokine CCL2
/ blood
Drug Resistance, Neoplasm
/ genetics
Female
Genes, erbB-1
Humans
Indoles
/ pharmacology
Lung Neoplasms
/ drug therapy
Male
Mice
Mice, Inbred BALB C
Middle Aged
Mutation
Quinolines
/ pharmacology
Retrospective Studies
Xenograft Model Antitumor Assays
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
10
04
2018
accepted:
29
11
2018
pubmed:
24
12
2018
medline:
10
10
2020
entrez:
23
12
2018
Statut:
epublish
Résumé
Anlotinib has been demonstrated in clinical trials to be effective in prolonging the progression-free survival (PFS) and overall survival (OS) of refractory advanced nonsmall cell lung cancer (NSCLC) patients. However, the underlying molecular mechanisms and predictive biomarkers of anlotinib are still unclear. A retrospective analysis of anlotinib administered to 294 NSCLC patients was performed to screen for underlying biomarkers of anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the antitumour molecular mechanisms of anlotinib. Changes in serum CCL2 levels were analysed to examine the correlation of the anlotinib response between responders and nonresponders. Anlotinib therapy was beneficial for prolonging OS in NSCLC patients harbouring positive driver gene mutations, especially patients harbouring the epithelial growth factor receptor (EGFR) Our study reports a novel anti-angiogenesis mechanism of anlotinib
Sections du résumé
BACKGROUND
Anlotinib has been demonstrated in clinical trials to be effective in prolonging the progression-free survival (PFS) and overall survival (OS) of refractory advanced nonsmall cell lung cancer (NSCLC) patients. However, the underlying molecular mechanisms and predictive biomarkers of anlotinib are still unclear.
METHODS
A retrospective analysis of anlotinib administered to 294 NSCLC patients was performed to screen for underlying biomarkers of anlotinib-responsive patients. Transcriptome and functional assays were performed to understand the antitumour molecular mechanisms of anlotinib. Changes in serum CCL2 levels were analysed to examine the correlation of the anlotinib response between responders and nonresponders.
RESULTS
Anlotinib therapy was beneficial for prolonging OS in NSCLC patients harbouring positive driver gene mutations, especially patients harbouring the epithelial growth factor receptor (EGFR)
CONCLUSIONS
Our study reports a novel anti-angiogenesis mechanism of anlotinib
Identifiants
pubmed: 30578392
pii: 13993003.01562-2018
doi: 10.1183/13993003.01562-2018
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
CCL2 protein, human
0
Chemokine CCL2
0
Indoles
0
Quinolines
0
anlotinib
0
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright ©ERS 2019.
Déclaration de conflit d'intérêts
Conflict of interest: J. Lu has nothing to disclose. Conflict of interest: H. Zhong has nothing to disclose. Conflict of interest: T. Chu has nothing to disclose. Conflict of interest: X. Zhang has nothing to disclose. Conflict of interest: R. Li has nothing to disclose. Conflict of interest: J. Sun has nothing to disclose. Conflict of interest: R. Zhong has nothing to disclose. Conflict of interest: Y. Yang has nothing to disclose. Conflict of interest: M.S. Alam has nothing to disclose. Conflict of interest: Y. Lou has nothing to disclose. Conflict of interest: J. Xu has nothing to disclose. Conflict of interest: Y. Zhang has nothing to disclose. Conflict of interest: J. Wu has nothing to disclose. Conflict of interest: X. Li has nothing to disclose. Conflict of interest: X. Zhao has nothing to disclose. Conflict of interest: K. Li has nothing to disclose. Conflict of interest: L. Lu has nothing to disclose. Conflict of interest: B. Han has nothing to disclose.