Deep Insight Section

Tumor growth and metastasis are dependent on neovascularization, which is mainly accomplished by the process of angiogenesis-sprouting of new microvessels from the existing blood vessels. To gain its ability of growth and invasiveness, malignant cells often express high levels of angiogenic factors that stimulate tumor angiogenesis and remodel tumor vessels. In addition to malignant cells, other host cells in the tumor microenvironment, including inflammatory cells, stromal fibroblasts and perivascular cells also significantly contribute to production of angiogenic factors and cytokines. Co-existence of various angiogenic factors and cytokines will inevitably cause interplay of various signaling pathways, leading to synergistic effects of tumor angiogenesis. Thus, therapeutic development of angiogenic factor inhibitors should be aimed to block not only the vertical signaling pathway triggered by a specific factor, but the horizontal interplay of various angiogenic pathways. This review discusses the mechanisms that underlie tumor angiogenesis, provides a few examples of angiogenic pathways that are commonly seen in most tumor types, and discusses the challenges of antiangiogenic cancer therapy.