Virtually every conventional cytotoxic drug has been found to be antiangiogenic in in vitro and in vivo models [18] . One treatment approach known as metronomic therapy uses frequent administrations of low-dose antiangiogenic agents to destroy vessels in tumors while decreasing the toxicity to normal tissues [19] [20] [21] . For example, it has been found in mice that frequent administration of relatively low, noncytotoxic doses of liposome-encapsulated doxorubicin can shrink various solid tumor xenografts [13, 16] . The antiangiogenic agent bevacizumab (Avastin), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been used with some success to treat advanced colon cancer. One study compared the effect using three chemotherapeutic agents alone to treat advanced colon cancer with using the three agents combined with bevacizumab [22] . They found that the combined use of chemotherapeutic agents and bevacizumab extended overall survival by approximately 4.7 months compared to the use of chemotherapeutic agents alone [22] . Other angiogenesis inhibitors, including sunitinib and sorafenib, have also been found to improve clinical outcomes when used to treat various cancer types [23, 24] . The targeting of proliferating endothelial cells in the blood vessels of tumors has several advantages. First, endothelial cells in malignant tumors are genetically stable, nonmalignant, and rarely drug resistant, compared to the cancer cells [19, 21] . However, some recent studies show that tumor-associated endothelial cells can acquire cytogenetic abnormalities while they are in the tumor microenvironment [25, 26] . Second, the destruction of endothelial cells using this method amplifies the drugs antitumor effect. It has been reported that the elimination of one endothelial cell can inhibit the growth of as many as a hundred tumor cells [27, 28] . Third, antiangiogenic therapy decreases IFP within the tumor allowing better penetration by chemotherapeutic agents [29] [30] [31] [32] . For example, Jain found that bevacizumab could decrease IFP by normalizing tumor vasculature and decreasing vascular leakage [29, 33] . Fourth, antiangiogenic therapy is known to inhibit the growth of both primary and metastatic solid tumors. Finally, intravenously injected angiogenesis inhibitors can directly reach endothelial cells.