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Updated: Jun 22, 2026

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
12:22

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer

John S P Yuen1, Erdem Akkaya, Yong Wang

  • 1Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Headington, Oxford, United Kingdom.

Molecular Cancer Therapeutics
|June 11, 2009
PubMed
Abstract

Insights

Targeting the type 1 insulin-like growth factor receptor (IGF1R) may overcome chemoresistance in clear cell renal cell cancer (CC-RCC). Depleting IGF1R sensitizes CC-RCC cells to chemotherapy and mTOR inhibitors, suggesting IGF1R as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Type 1 insulin-like growth factor receptor (IGF1R) expression is linked to poor prognosis in clear cell renal cell cancer (CC-RCC).
  • IGF1R is upregulated in CC-RCC due to frequent inactivation of the von Hippel-Lindau (VHL) tumor suppressor.
  • VHL inactivation is a key event in CC-RCC pathogenesis, leading to increased IGF1R signaling.

Purpose of the Study:

  • To investigate if IGF1R upregulation contributes to therapeutic resistance in CC-RCC.
  • To evaluate the effect of IGF1R depletion on sensitivity to cytotoxic drugs and mTOR inhibitors.
  • To determine if targeting IGF1R can enhance the efficacy of existing cancer treatments.

Main Methods:

  • Utilized CC-RCC cell lines with mutant and functional VHL.
  • Employed small interfering RNA (siRNA) to deplete IGF1R expression.
  • Assessed sensitivity to cytotoxic agents (5-fluorouracil, etoposide) and the mTOR inhibitor rapamycin.
  • Administered stabilized IGF1R siRNA in vivo to CC-RCC xenografts.

Main Results:

  • CC-RCC cells with higher IGF1R and mutant VHL exhibited greater chemoresistance.
  • IGF1R depletion induced apoptosis, inhibited cell survival, and sensitized cells to chemotherapy.
  • IGF1R inhibition enhanced sensitivity to mTOR inhibitors by suppressing rapamycin-induced Akt activation.
  • In vivo administration of IGF1R siRNA sensitized CC-RCC xenografts to rapamycin.

Conclusions:

  • IGF1R is a validated therapeutic target in clear cell renal cell cancer.
  • Inhibition of IGF1R can overcome chemoresistance and enhance sensitivity to mTOR inhibitors.
  • Clinical evaluation of IGF1R-inhibitory drugs is warranted for patients with renal cancer.

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