RT Journal Article
SR Electronic
T1 PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1943
OP 1951
DO 10.21873/anticanres.14149
VO 40
IS 4
A1 YOHEI SEKINO
A1 TAKESHI HAGURA
A1 XIANGRUI HAN
A1 TAKASHI BABASAKI
A1 KEISUKE GOTO
A1 SHOGO INOUE
A1 TETSUTARO HAYASHI
A1 JUN TEISHIMA
A1 MASANOBU SHIGETA
A1 DAIKI TANIYAMA
A1 KAZUYA KURAOKA
A1 KAZUHIRO SENTANI
A1 WATARU YASUI
A1 AKIO MATSUBARA
YR 2020
UL http://ar.iiarjournals.org/content/40/4/1943.abstract
AB 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.