Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study aimed to examine the role of CD44 in sunitinib resistance and as a predictive marker in mRCC.
We analyzed the effect of CD44 knockdown on sunitinib resistance in RCC cell lines using WST-1 assays. CD44 expression in mRCC patients treated with first-line sunitinib was determined by immunohistochemistry. We validated the findings of this study by in silico analysis.
CD44 knockdown increased sensitivity to sunitinib. Immunohistochemical analysis revealed that 19 (34.5%) of 55 mRCC cases were positive for CD44. CD44-positive cases were associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, high CD44 expression was significantly associated with poor PFS after sunitinib but not after avelumab + axitinib therapy.
CD44 is involved in sunitinib resistance and may be a promising marker for sunitinib treatment in mRCC.
Anticancer research. 2021 Oct [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.