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P53 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma.
Sekino, Yohei; Takemoto, Kenshiro; Murata, Daiki; Babasaki, Takashi; Kobatake, Kohei; Kitano, Hiroyuki; Ikeda, Kenichiro; Goto, Keisuke; Inoue, Shogo; Hayashi, Tetsutaro; Taniyama, Daiki; Shigeta, Masanobu; Kuraoka, Kazuya; Mita, Koji; Kaneko, Mayumi; Sentani, Kazuhiro; Oue, Naohide; Teishima, Jun.
Affiliation
  • Sekino Y; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; akikosekino@gmail.com.
  • Takemoto K; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Murata D; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Babasaki T; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Kobatake K; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Kitano H; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Ikeda K; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Goto K; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Inoue S; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Hayashi T; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Taniyama D; Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Shigeta M; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Kuraoka K; Department of Urology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
  • Mita K; Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
  • Kaneko M; Department of Urology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan.
  • Sentani K; Department of Diagnostic Pathology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan.
  • Oue N; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
  • Teishima J; Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Anticancer Res ; 41(9): 4287-4294, 2021 Sep.
Article in En | MEDLINE | ID: mdl-34475048
ABSTRACT
BACKGROUND/

AIM:

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. MATERIALS AND

METHODS:

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.

RESULTS:

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.

CONCLUSION:

p53 may be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Piperazines / Carcinoma, Renal Cell / Up-Regulation / Tumor Suppressor Protein p53 / Drug Resistance, Neoplasm / Sunitinib / Imidazoles / Kidney Neoplasms Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Anticancer Res Year: 2021 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Piperazines / Carcinoma, Renal Cell / Up-Regulation / Tumor Suppressor Protein p53 / Drug Resistance, Neoplasm / Sunitinib / Imidazoles / Kidney Neoplasms Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Anticancer Res Year: 2021 Document type: Article