PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma.
Biomarkers, Tumor
/ genetics
CRISPR-Cas Systems
Carcinoma, Renal Cell
/ drug therapy
Drug Resistance, Neoplasm
/ drug effects
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Knockout Techniques
Humans
Kaplan-Meier Estimate
Male
PTEN Phosphohydrolase
/ genetics
Progression-Free Survival
Protein Kinase Inhibitors
/ pharmacology
Sorafenib
/ pharmacology
Spheroids, Cellular
/ drug effects
Sunitinib
/ pharmacology
PTEN
Renal cell carcinoma
sorafenib
spheroid
sunitinib
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
11
02
2020
revised:
25
02
2020
accepted:
27
02
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
10
4
2020
Statut:
ppublish
Résumé
Targeted receptor tyrosine kinase inhibitor (TKI) is a standard treatment in advanced renal cell carcinoma (RCC). However, the role of PTEN in TKI resistance remains poorly understood. We aimed to determine the functional role of PTEN knockout and analyse the predictive significance of PTEN expression for TKI treatment in RCC. We developed PTEN knockout cells in RCC cell lines using the CRISPR-Cas9 system and analysed the effect of PTEN knockout on spheroid formation and resistance to sunitinib and sorafenib. PTEN knockout promoted spheroid formation and decreased sunitinib/sorafenib sensitivity in RCC cell lines. PTEN immunohistochemistry in 74 metastatic RCCs treated with sunitinib and sorafenib revealed negative PTEN expression in 23% of samples. Kaplan-Meier analysis showed a significant association of negative PTEN expression with poor progression-free survival in metastatic RCC treated with sunitinib and sorafenib (p=0.024) or sunitinib alone (p=0.009). PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Targeted receptor tyrosine kinase inhibitor (TKI) is a standard treatment in advanced renal cell carcinoma (RCC). However, the role of PTEN in TKI resistance remains poorly understood. We aimed to determine the functional role of PTEN knockout and analyse the predictive significance of PTEN expression for TKI treatment in RCC.
MATERIALS AND METHODS
METHODS
We developed PTEN knockout cells in RCC cell lines using the CRISPR-Cas9 system and analysed the effect of PTEN knockout on spheroid formation and resistance to sunitinib and sorafenib.
RESULTS
RESULTS
PTEN knockout promoted spheroid formation and decreased sunitinib/sorafenib sensitivity in RCC cell lines. PTEN immunohistochemistry in 74 metastatic RCCs treated with sunitinib and sorafenib revealed negative PTEN expression in 23% of samples. Kaplan-Meier analysis showed a significant association of negative PTEN expression with poor progression-free survival in metastatic RCC treated with sunitinib and sorafenib (p=0.024) or sunitinib alone (p=0.009).
CONCLUSION
CONCLUSIONS
PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.
Identifiants
pubmed: 32234883
pii: 40/4/1943
doi: 10.21873/anticanres.14149
doi:
Substances chimiques
Biomarkers, Tumor
0
Protein Kinase Inhibitors
0
Sorafenib
9ZOQ3TZI87
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Sunitinib
V99T50803M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1943-1951Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.