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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

Resistance to targeted therapy in renal-cell carcinoma

Brian I Rini1, Michael B Atkins

  • 1Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Glickman Urologic and Kidney Institute, 9500 Euclid Avenue/Desk R35, Cleveland, OH 44195, USA. rinib2@ccf.org

The Lancet. Oncology
|October 3, 2009
PubMed

Insights

Targeted therapies for metastatic renal-cell carcinoma (RCC) involving vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) show promise. Understanding resistance mechanisms is key to improving patient outcomes with combination therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Metastatic renal-cell carcinoma (RCC) treatment has been revolutionized by targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways.
  • However, intrinsic and acquired resistance to these targeted therapies limits their long-term efficacy in many patients.

Purpose of the Study:

  • To investigate the biological basis of resistance to VEGF and mTOR targeted therapies in metastatic RCC.
  • To explore potential combination or sequential therapeutic strategies to overcome resistance.

Main Methods:

  • Review of emerging preclinical evidence on resistance mechanisms.
  • Analysis of clinical data supporting activity of agents in resistant populations.
  • Identification of key signaling pathways (e.g., HIF, AKT) involved in resistance.

Main Results:

  • Preclinical data suggest resistance arises from tumor and environmental changes, enabling VEGF-independent growth.
  • Pathways upstream of receptor blockade (HIF, AKT) and independent pathways can drive tumor progression despite therapy.
  • Clinical data indicate activity of certain agents in resistant RCC patients.

Conclusions:

  • Understanding resistance mechanisms to VEGF and mTOR inhibitors is crucial for optimizing metastatic RCC treatment.
  • Combination or sequential therapies targeting alternative pathways (HIF, AKT) are rational approaches.
  • Ongoing clinical trials are evaluating novel strategies to overcome resistance and improve outcomes.

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