PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma.

Abstract

BACKGROUND/AIM:

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:

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:

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:

PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.

• Authors: Yohei Sekino, Takeshi Hagura, Xiangrui Han, Takashi Babasaki, Keisuke Goto, Shogo Inoue, Tetsutaro Hayashi, Jun Teishima, Masanobu Shigeta, Daiki Taniyama, Kazuya Kuraoka, Kazuhiro Sentani, Wataru Yasui, Akio Matsubara
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 4 Pg. 1943-1951 (Apr 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 32234883 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Biomarkers, Tumor
• Protein Kinase Inhibitors
• Sorafenib
• PTEN Phosphohydrolase
• PTEN protein, human
• Sunitinib

Topics

• Biomarkers, Tumor (genetics)
• CRISPR-Cas Systems
• Carcinoma, Renal Cell (drug therapy, genetics, pathology)
• 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)