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Updated: May 18, 2026

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
06:38

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

Published on: April 12, 2017

c-Met is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma

G T Gibney1, S A Aziz2, R L Camp3

  • 1Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|October 2, 2012
PubMed
Abstract

Insights

c-Met pathway activation is linked to poor prognosis in renal cell carcinoma (RCC). Inhibiting c-Met shows promise for treating clear cell RCC, warranting further investigation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The c-Met pathway is implicated in various cancers, but its role in clear cell renal cell carcinoma (ccRCC) requires further elucidation.
  • This study investigates c-Met expression and its therapeutic inhibition in a large cohort of renal cell carcinoma (RCC) tumors and cell lines.

Purpose of the Study:

  • To determine the expression patterns of c-Met in different subtypes of RCC.
  • To assess the correlation between c-Met expression and patient prognosis.
  • To evaluate the efficacy of c-Met inhibitors in clear cell RCC cell lines.

Main Methods:

  • c-Met protein expression was quantified using automated quantitative analysis (AQUA) on a tissue microarray of 330 RCC tumors.
  • Expression levels were compared between RCC subtypes and adjacent normal renal tissue.
  • In vitro studies involved assessing c-Met inhibition using SU11274 and ARQ 197 in clear cell RCC cell lines.

Main Results:

  • c-Met expression was significantly higher in all RCC subtypes compared to normal tissue (P < 0.0001).
  • Elevated c-Met expression was associated with papillary and sarcomatoid subtypes, as well as high-grade and advanced-stage tumors.
  • Higher c-Met expression independently predicted worse disease-specific survival (HR=1.36, P=0.0091), even in clear cell RCC subsets.
  • c-Met inhibition with SU11274 and ARQ 197 effectively blocked proliferation and colony formation in clear cell RCC cell lines.

Conclusions:

  • c-Met pathway activation is associated with adverse pathologic features and a poorer prognosis in renal cell carcinoma.
  • Targeting the c-Met pathway with inhibitors like ARQ 197 demonstrates in vitro efficacy against clear cell RCC.
  • Further clinical investigation of ARQ 197, incorporating biomarker studies, is recommended for RCC treatment.

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