Related Experiment Video

Updated: Dec 1, 2025

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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Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade

Robert J Motzer1, Romain Banchereau2, Habib Hamidi2

  • 1Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Cancer Cell
|November 6, 2020
PubMed

Insights

This study analyzed 823 advanced renal cell carcinoma (RCC) tumors, revealing molecular subtypes that predict response to anti-angiogenesis and immunotherapy. Tailoring treatments based on these subtypes can improve patient outcomes.

Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • Advanced renal cell carcinoma (RCC) treatment response varies significantly.
  • Understanding molecular drivers is crucial for personalized therapy in RCC.

Purpose of the Study:

  • To identify molecular subsets in advanced RCC patients.
  • To correlate these subsets with clinical outcomes of angiogenesis blockade and checkpoint inhibitors.
  • To explore the impact of specific mutations and tumor characteristics on treatment response.

Main Methods:

  • Integrated multi-omics analysis of 823 advanced RCC tumors.
  • Unsupervised transcriptomic analysis to define molecular subsets.
  • Correlation of molecular features with clinical outcomes and somatic mutations.

Main Results:

  • Seven distinct molecular subsets identified, characterized by unique angiogenesis, immune, cell-cycle, metabolism, and stromal programs.
  • Sunitinib and atezolizumab + bevacizumab showed efficacy in high-angiogenesis subsets.
  • Atezolizumab + bevacizumab demonstrated improved benefit in tumors with high T-effector and/or cell-cycle transcription.
  • Specific mutations (PBRM1, KDM5C, CDKN2A/B, TP53) were associated with distinct molecular programs and metabolic pathways.
  • Sarcomatoid tumors showed unique molecular profiles, including lower angiogenesis markers and increased PD-L1 expression.

Conclusions:

  • Molecular stratification of RCC patients can predict treatment response to angiogenesis inhibitors and checkpoint inhibitors.
  • Findings explain differential outcomes observed in sarcomatoid tumors.
  • Results support the development of personalized therapeutic strategies for RCC.
Keywords:
CDKN2A/BPBRM1PD-L1VHLatezolizumabbevacizumabcheckpoint blockadeintegrated genomicsrenal cell carcinomasarcomatoidsunitinib

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