Targeting the VEGF signaling pathway in cancer therapy.

INTRODUCTION: Angiogenesis was first proposed as a possible target for the treatment of human cancer several decades ago. During recent years, the discovery of VEGF as the main mediator of tumor angiogenesis enabled the specific and successful inhibition of angiogenesis in several experimental and clinical studies. AREAS COVERED: This review discusses recent data regarding the molecular mechanisms of VEGF signaling in cancer development, the response of various types of human cancer to anti-VEGF treatment, reasons for a failure of therapy and possible biomarkers for the prediction of therapeutic response. The literature discussed is based on a systematic analysis using PubMed and MEDLINE databases for articles presented in 2000 - 2011. EXPERT OPINION: Although anti-VEGF therapy has improved the treatment of several types of cancer during recent years, several questions still remain unanswered. For instance, in some patients, cancer develops resistance to anti-VEGF therapeutics following initially successful therapy, whereas others never show a response. Therefore, a more detailed knowledge of the molecular mechanisms involved in VEGF signaling and predictive biomarkers for a response to anti-VEGF therapy are among the most important challenges for VEGF research today.