Biomarkers for VEGF and mTOR Blockade in Advanced Renal Cancer

Summary

Principal Investigator: Jaime R Merchan
Abstract: [unreadable] DESCRIPTION (provided by applicant): Blockade of angiogenic and non-angiogenic pathways is a promising strategy that has the potential to provide significant benefit to patients with advanced renal cell carcinoma (RCC). In order to individualize targeted therapies to the appropriate patients, it is necessary to identify and validate markers correlated with clinical benefit and/or toxicity. Preclinical studies have led us to a phase I/II trial of Bevacizumab and CCI- 779 to determine the safety and efficacy of the combination in patients with advanced RCC. We have observed very encouraging clinical antitumor activity from the first cohort of patients in the phase I portion of the study. Our long term goals are to identify and validate biomarkers predictive of clinical benefit as well as markers that can be used as surrogate endpoints of activity and toxicity in patients with advanced renal cell cancer treated with antiangiogenic therapies. Specific Aim 1: To identify tumor molecular markers associated with clinical benefit to the combination of CCI-779 and Bevacizumab in patients with metastatic renal cell cancer. Specific Aim 2: To evaluate circulating biomarkers associated with response and toxicity to the combination of CCI-779 and Bevacizumab in advanced renal cell cancer. Our proposal takes advantage of the current understanding of the molecular mechanisms of renal cell carcinoma and the availability of targeted agents that are active against this disease. Data generated in this study may help identify patients who will benefit from this treatment based on the molecular features of their tumors, a step forward in the development of individualized treatments for advanced renal cell carcinoma. Our proposed circulating biomarker studies will assess the effects of the treatment on different aspects of tumor neovascularization and may help identify patients at risk for toxicity from antiangiogenic treatments. This information will be extremely useful for the design of future trials using these agents in renal and other cancers and for future clinical practice. [unreadable] [unreadable] [unreadable]
Funding Period: 2006-09-19 - 2009-08-31
more information: NIH RePORT

Top Publications

  1. pmc Antiangiogenic activity of 2-deoxy-D-glucose
    Jaime R Merchan
    Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida, United States of America
    PLoS ONE 5:e13699. 2010
  2. pmc 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3beta and a tumor suppressor in lung cancer
    Guosheng Huang
    Department of Pathology, Division of Hematology Oncology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Cancer Res 68:5040-8. 2008
  3. pmc Tumor and vascular targeting of a novel oncolytic measles virus retargeted against the urokinase receptor
    Yuqi Jing
    Division of Hematology Oncology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida 33136, USA
    Cancer Res 69:1459-68. 2009

Scientific Experts

  • Jaime R Merchan
  • Yuqi Jing
  • Guosheng Huang
  • Takafumi Nakamura
  • Ianko Iankov
  • Jin Zhang
  • Stephen J Russell
  • Caili Tong
  • Ester Lowenberg
  • Stefano Monti
  • Min Yan
  • Daniel G Tenen
  • Rosana Eisenberg
  • Earl Lawrence
  • Todd Golub
  • Sanford D Markowitz
  • Pingfu Fu
  • Jaclyn Walbroehl
  • Balazs Halmos

Detail Information

Publications3

  1. pmc Antiangiogenic activity of 2-deoxy-D-glucose
    Jaime R Merchan
    Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida, United States of America
    PLoS ONE 5:e13699. 2010
    ..Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated...
  2. pmc 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3beta and a tumor suppressor in lung cancer
    Guosheng Huang
    Department of Pathology, Division of Hematology Oncology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Cancer Res 68:5040-8. 2008
    ..In summary, we identify 15-PGDH as a direct downstream effector of HNF3beta and show that 15-PGDH acts as a tumor suppressor in lung cancer...
  3. pmc Tumor and vascular targeting of a novel oncolytic measles virus retargeted against the urokinase receptor
    Yuqi Jing
    Division of Hematology Oncology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida 33136, USA
    Cancer Res 69:1459-68. 2009
    ..This is the first retargeted oncolytic MV able to replicate in murine cells and target tumor vasculature in a uPAR-dependent manner...