TY - JOUR T1 - PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma JF - Anticancer Research JO - Anticancer Res SP - 1943 LP - 1951 DO - 10.21873/anticanres.14149 VL - 40 IS - 4 AU - YOHEI SEKINO AU - TAKESHI HAGURA AU - XIANGRUI HAN AU - TAKASHI BABASAKI AU - KEISUKE GOTO AU - SHOGO INOUE AU - TETSUTARO HAYASHI AU - JUN TEISHIMA AU - MASANOBU SHIGETA AU - DAIKI TANIYAMA AU - KAZUYA KURAOKA AU - KAZUHIRO SENTANI AU - WATARU YASUI AU - AKIO MATSUBARA Y1 - 2020/04/01 UR - http://ar.iiarjournals.org/content/40/4/1943.abstract N2 - 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. ER -