Future prospects and challenges of antiangiogenic cancer gene therapy.

In 1971 Judah Folkman proposed the concept of antiangiogenesis as a therapeutic target for cancer. More than 30 years later, concept became reality with the approval of the antivascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab as a first-line treatment for metastatic colorectal cancer. Monoclonal antibodies and small molecular drugs are the most widely applied methods for inhibition of angiogenesis. The efficacy of these antiangiogenic modalities has been proven, in both preclinical and clinical settings. Although angiogenesis plays a major role in wound healing, hypoxia, and in the female reproductive cycle, inhibition of angiogenesis seems to be a relatively safe therapeutic option against cancers, and has therefore become a logical arena for a wide range of experimentation. The twentieth century has shown the boom of gene therapy and thus it has been applied also in the antiangiogenic setting. This review summarizes methods to induce antiangiogenic responses with gene therapy and discusses the obstacles and future prospects of antiangiogenic cancer gene therapy.