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Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

The Quest for Surrogate Markers of Angiogenesis: A Paradigm for Translational Research in Tumor Angiogenesis and Anti- Angiogenesis Trials

Author(s): Curzio Ruegg, Jean-Yves Meuwly, Robert Driscoll, Patricia Werffeli, Khalil Zaman and Roger Stupp

Volume 3, Issue 8, 2003

Page: [673 - 691] Pages: 19

DOI: 10.2174/1566524033479410

Price: $65


Inhibition of tumor angiogenesis suppresses tumor growth and metastatic spreading in many experimental models, suggesting that anti-angiogenic drugs may be used to treat human cancer. During the past decade more than eighty molecules that showed anti-angiogenic activity in preclinical studies were tested in clinical cancer trials, but most of them failed to demonstrate any measurable anti-tumor activity and none have been approved for clinical use. Recent results stemming from trials with anti-VEGF antibodies, used alone or in combination with chemotherapy, suggest that systemic anti-angiogenic therapy may indeed have a measurable impact on cancer progression and patient survival. From the clinical studies it became nevertheless clear that the classical endpoints used in anti-cancer trials do not bring sufficient discriminative power to monitor the effects of anti-angiogenic drugs. It is therefore necessary to identify and validate molecular, cellular and functional surrogate markers of angiogenesis to monitor activity and efficacy of anti-angiogenic drugs in patients. Availability of such markers will be instrumental to re-evaluate the role of tumor angiogenesis in human cancer, to identify new molecular targets and drugs, and to improve planning, monitoring and interpretation of future studies. Future anti-angiogenesis trials integrating biological endpoints and surrogate markers or angiogenesis will require close collaboration between clinical investigators and laboratory-based researchers. Here we review and discuss critical issues and emerging paradigms relevant to tumor angiogenesis and anti-angiogenic drugs and to the monitoring of tumor angiogenesis and anti-angiogenic effects in patients.

Keywords: surrogate markers, angiogenesis, translational research, tumor angiogenesis, metastatic, anti-angiogenic drugs, anti-vegf antibodies

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