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CD44 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma.

Authors
  • Sekino, Yohei1
  • Takemoto, Kenshiro2
  • Murata, Daiki2
  • Babasaki, Takashi2, 3
  • Kobatake, Kohei2
  • Kitano, Hiroyuki2
  • Ikeda, Kenichiro2
  • Goto, Keisuke2
  • Inoue, Shogo2
  • Hayashi, Tetsutaro2
  • Taniyama, Daiki3
  • Shigeta, Masanobu4
  • Kuraoka, Kazuya5
  • Mita, Koji6
  • Kaneko, Mayumi7
  • Sentani, Kazuhiro3
  • Oue, Naohide3
  • Teishima, Jun2
  • 1 Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; [email protected] , (Japan)
  • 2 Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. , (Japan)
  • 3 Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. , (Japan)
  • 4 Department of Urology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan. , (Japan)
  • 5 Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan. , (Japan)
  • 6 Department of Urology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan. , (Japan)
  • 7 Department of Diagnostic Pathology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan. , (Japan)
Type
Published Article
Journal
Anticancer Research
Publisher
International Institute of Anticancer Research
Publication Date
Oct 01, 2021
Volume
41
Issue
10
Pages
4875–4883
Identifiers
DOI: 10.21873/anticanres.15301
PMID: 34593435
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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