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PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma

Yohei Sekino1, Takeshi Hagura2, Xiangrui Han2

  • 1Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan akikosekino@gmail.com.

Anticancer Research
|April 3, 2020
PubMed
Abstract

Insights

Loss of PTEN in renal cell carcinoma (RCC) promotes resistance to targeted therapies like sunitinib and sorafenib. Negative PTEN expression predicts poor progression-free survival in metastatic RCC patients treated with TKIs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Targeted therapies, including receptor tyrosine kinase inhibitors (TKIs), are standard treatments for advanced renal cell carcinoma (RCC).
  • The role of PTEN (Phosphatase and tensin homolog) in TKI resistance in RCC is not well understood.
  • Understanding PTEN's function is crucial for improving TKI efficacy in RCC treatment.

Purpose of the Study:

  • To investigate the functional role of PTEN knockout in RCC.
  • To analyze the predictive significance of PTEN expression for TKI treatment outcomes in RCC.
  • To explore PTEN as a potential biomarker and therapeutic target in metastatic RCC.

Main Methods:

  • PTEN knockout RCC cell lines were generated using the CRISPR-Cas9 system.
  • The impact of PTEN knockout on spheroid formation and sensitivity to sunitinib and sorafenib was assessed.
  • PTEN expression was evaluated via immunohistochemistry in 74 metastatic RCC samples.

Main Results:

  • PTEN knockout enhanced spheroid formation and reduced sensitivity to sunitinib and sorafenib in RCC cell lines.
  • Negative PTEN expression was observed in 23% of metastatic RCC samples.
  • Kaplan-Meier analysis revealed that negative PTEN expression was significantly associated with poorer progression-free survival in patients treated with TKIs.

Conclusions:

  • PTEN plays a significant role in TKI resistance in renal cell carcinoma.
  • Loss of PTEN expression is linked to unfavorable treatment outcomes in metastatic RCC.
  • PTEN represents a potential predictive biomarker and therapeutic target for TKI treatment in metastatic RCC.
Keywords:
PTENRenal cell carcinomasorafenibspheroidsunitinib

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