The quest for surrogate markers of angiogenesis: a paradigm for translational research in tumor angiogenesis and anti-angiogenesis trials

Abstract

Inhibition of tumor angiogenesis suppresses tumor growth and metastatic spreading in many expérimental models, suggesting that anti-angiogenic drugs may be used to treat human cancer. During the past décade more than eighty molécules that showed anti-angiogenic activity in preclinical studies were tested in clinical cancer trials, but most of them failed to demonstrate any measurable antitum or 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 interprétation 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.