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Updated: Jul 19, 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

Molecular pathways in renal cell carcinoma--rationale for targeted treatment

William Y Kim1, William G Kaelin

  • 1Department of Hematology Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Seminars in Oncology
|October 19, 2006
PubMed

Insights

Loss of the VHL tumor suppressor gene in kidney cancer leads to increased hypoxia-inducible factor (HIF). Inhibiting HIF and its downstream targets shows promise for treating clear cell renal carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Clear cell renal carcinoma (RCC) frequently involves mutations or silencing of the VHL tumor-suppressor gene.
  • Loss of pVHL function leads to stabilization of hypoxia-inducible factor (HIF).
  • Stabilized HIF enhances the transcription of genes involved in tumorigenesis.

Purpose of the Study:

  • To investigate the role of HIF in clear cell renal carcinoma growth.
  • To review therapeutic strategies targeting HIF and its downstream effectors in kidney cancer.

Main Methods:

  • Preclinical models were used to assess the effect of HIF downregulation on renal carcinoma cell growth.
  • Literature review of targeted therapies inhibiting HIF or its responsive gene products (VEGF, PDGF).

Main Results:

  • Downregulation of HIF is sufficient to suppress human renal carcinoma cell growth in preclinical models.
  • Direct inhibition of HIF with drugs remains challenging.
  • Indirect inhibitors of HIF (e.g., mTOR inhibitors) and drugs targeting HIF-responsive products (VEGF, PDGF) show significant activity in kidney cancer.

Conclusions:

  • Targeted therapies inhibiting HIF pathway components represent significant advances in kidney cancer treatment.
  • Ongoing clinical trials are exploring optimal combinations of these targeted agents with each other and with conventional therapies.

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