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Updated: Jan 29, 2026

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

Published on: January 22, 2013

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Implementing Reverse Phase Protein Array Profiling as a Sensitive Method for the Early Pre-Clinical Detection of

Alice C O'Farrell1, Ian S Miller1, Rhys Evans1

  • 1RCSI Centre for Systems Medicine, Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, D02 HX03, Ireland.

Proteomics. Clinical Applications
|February 16, 2019
PubMed
Abstract

Insights

Sunitinib, a cancer drug, causes side effects by inhibiting kinases in non-cancerous tissues. This study used protein arrays to identify early molecular signs of sunitinib toxicity in mouse organs.

Area of Science:

  • Oncology
  • Pharmacology
  • Toxicology

Background:

  • Sunitinib is a multi-targeted tyrosine kinase inhibitor (TKI) used in cancer treatment.
  • TKIs can cause significant side effects, potentially due to inhibiting kinases in healthy tissues.
  • Understanding these off-target effects is crucial for patient safety.

Purpose of the Study:

  • To investigate the molecular mechanisms of sunitinib's off-target toxicities.
  • To identify early molecular indicators of sunitinib-induced organ damage in pre-clinical models.

Main Methods:

  • Mice were treated with sunitinib (40 mg/kg) for 4 weeks.
  • Reverse Phase Protein Array (RPPA) was used for protein expression analysis in various organs.
  • Histopathological examination was performed for correlation.

Main Results:

  • Differentially expressed proteins related to stress and damage were found in most organs.
  • Heart tissue showed proteins linked to myocardial hypertrophy, ischemia/reperfusion, and hypoxia, though histology was normal.
  • Skin tissue exhibited proteins associated with inflammation and keratinocyte hyper-proliferation.

Conclusions:

  • A combined RPPA and histopathology approach can detect early signs of TKI toxicity.
  • This method helps elucidate the mechanisms of on-target/off-target toxicities.
  • Early detection of molecular changes can inform strategies to mitigate TKI side effects.
Keywords:
off-target toxicitypreclinical modelsreverse phase protein arrayssunitinibtyrosine kinase inhibitors

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