Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study examined the potential role of p53 in sunitinib resistance and as a predictive marker in mRCC.
We analysed the effects of p53 knockout on sunitinib resistance. p53 expression in 53 mRCC patients receiving first-line sunitinib was determined immunohistochemically. We performed in silico analysis to examine the predictive value of p53 in mRCC.
WST-1 assays showed that p53 knockout decreased sensitivity to sunitinib. Sunitinib and nutlin-3 together suppressed cell growth. Immunohistochemistry revealed 11 p53-positive cases among 53 patients with mRCC. Kaplan-Meier analysis showed that p53-positive cases tended to be associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, TP53 mutation was significantly associated with poor PFS after sunitinib treatment.
p53 may be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC.
Anticancer research. 2021 Sep [Epub]
Yohei Sekino, Kenshiro Takemoto, Daiki Murata, Takashi Babasaki, Kohei Kobatake, Hiroyuki Kitano, Kenichiro Ikeda, Keisuke Goto, Shogo Inoue, Tetsutaro Hayashi, Daiki Taniyama, Masanobu Shigeta, Kazuya Kuraoka, Koji Mita, Mayumi Kaneko, Kazuhiro Sentani, Naohide Oue, Jun Teishima
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; ., Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Department of Urology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan., Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan., Department of Urology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan., Department of Diagnostic Pathology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan.