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Updated: Feb 24, 2026

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

Published on: April 12, 2017

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Combination therapy using molecular-targeted drugs modulates tumor microenvironment and impairs tumor growth in renal

Hiroyuki Kitano1, Yasuhiko Kitadai2, Jun Teishima1

  • 1Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.

Cancer Medicine
|August 24, 2017
PubMed

Insights

Combining platelet-derived growth factor receptor (PDGF-R) and mammalian target of rapamycin (mTOR) inhibitors effectively targets kidney cancer stroma and growth. This combination therapy shows promise for treating kidney cancer by disrupting tumor-stromal interactions.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor growth and metastasis involve cancer cells and stromal cells, many expressing platelet-derived growth factor receptors (PDGF-Rs).
  • PI3K-AKT-mammalian target of rapamycin (mTOR) signaling is frequently activated in various cancers, regulating cell growth, metabolism, and angiogenesis.

Purpose of the Study:

  • To investigate the impact of PDGF-R and mTOR inhibitors on kidney cancer stroma.
  • To evaluate the efficacy of combination therapy using these inhibitors against kidney cancer.

Main Methods:

  • Utilized an orthotopic mouse model of human kidney cancer.
  • Administered sunitinib (PDGF-R inhibitor) and everolimus (mTOR inhibitor) individually and in combination.
  • Assessed tumor growth, stromal reactivity, microvessel density, and pericyte coverage.

Main Results:

  • Sunitinib decreased stromal reactivity, microvessel density, and pericyte coverage but did not suppress tumor growth.
  • Everolimus decreased tumor growth and microvessel density but did not affect stromal reactivity.
  • Combination therapy with sunitinib and everolimus reduced both tumor growth rate and stromal reactivity.

Conclusions:

  • Targeting cancer-stromal cell interactions with molecular agents is a promising antitumor strategy.
  • Combination therapy with PDGF-R and mTOR inhibitors demonstrates enhanced efficacy in reducing kidney cancer growth and stromal reaction.
  • Inhibition of the cancer-stromal axis offers a potential therapeutic approach for kidney cancer.
Keywords:
Combination therapyPDGF-Rrenal cell carcinomastromal celltumor microenvironment

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