One third of patients newly diagnosed with renal cell carcinoma (RCC) have metastatic disease. Of patients initially diagnosed with localized RCC, one third will eventually develop metastatic disease despite treatment of the primary tumor. RCC is resistant to conventional chemotherapies and radiation, and generalized cytokine stimulation with interferon-alpha (IFN-1) or interleukin-2 (IL2) represents effective treatment for metastatic RCC. Recent advances in understanding of the disease mechanism have allowed development of more specific treatments. Clear cell RCC is characterized by von Hippel Lindau (VHL) gene mutation, which results in overexpression of downstream gene products such as vascular endothelial growth factor (VEGF). Bevacizumab is a monoclonal antibody that binds and neutralizes all isoforms of the VEGF protein and is being investigated in clinical trials of advanced RCC. CALGB 90206 randomized untreated, metastatic clear cell RCC patients to IFN-1 alone or IFN-1 plus bevacizumab. The study is now closed to enrollment after reaching its target accrual of over 700 patients. As part of the study, pre-treatment paraffin RCC tumor blocks were banked for correlative studies. This large repository of tumor tissue with linked clinical outcome represents a valuable resource for advancing the science of gene expression as a predictive and prognostic tool. We propose using a quantitative, reverse transcription PCR based approach to assess mRNA levels for relevant genes. Gene expression levels are used to develop models for predicting response to treatment, determining prognosis, and assessing the variability in molecular defects associated with RCC. Insights from this analysis will have broad implications across solid tumors and across multiple anti-angiogenic modalities. Treatments for kidney cancer include immune modulation and inhibition of new blood vessel formation. This study uses tumor tissue collected as part of CALGB 90206, a clinical trial for advanced kidney cancer evaluating immunotherapy with or without inhibition of blood vessel formation, to identify molecular markers that can predict survival and response to treatment.

Public Health Relevance

Treatments for kidney cancer include immune modulation and inhibition of new blood vessel formation. This study uses tumor tissue collected as part of CALGB 90206, a clinical trial for advanced kidney cancer evaluating immunotherapy with or without inhibition of blood vessel formation, to identify molecular markers that can predict survival and response to treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA133072-06
Application #
8312591
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Song, Min-Kyung H
Project Start
2008-08-01
Project End
2014-06-30
Budget Start
2012-09-12
Budget End
2013-06-30
Support Year
6
Fiscal Year
2012
Total Cost
$343,754
Indirect Cost
$122,080
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Li, Ping; Grigorenko, Elena; Funari, Vince et al. (2013) Evaluation of a high-throughput, microfluidics platform for performing TaqMan™ qPCR using formalin-fixed paraffin-embedded tumors. Bioanalysis 5:1623-33
Glenn, Sean T; Head, Karen L; Teh, Bin T et al. (2010) Maximizing RNA yield from archival renal tumors and optimizing gene expression analysis. J Biomol Screen 15:80-5
Hellenthal, Nicholas J; Underwood, Willie; Penetrante, Remedios et al. (2010) Prospective clinical trial of preoperative sunitinib in patients with renal cell carcinoma. J Urol 184:859-64