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Given these findings, coupling agents that block the VEGF pathway with agents targeting the Notch pathway may result in enhanced treatment efficacy. Combined therapy may therefore overcome the issue of tumor escape that is associated with single-agent treatments. Evidence of this benefit was
demonstrated when anti-DLL4 antibody was combined with VEGF inhibition in human lung carcinoma and mouse leukemia tumor models. In both studies,
combined therapy resulted in enhanced tumor growth inhibition as compared to either monotherapy.It has also been shown that human sarcoma xenograft
tumors in mice that are unresponsive to VEGF inhibition are instead responsive to DLL4 blocking antibody.These data further exemplify the crosstalk between VEGF and the Notch signaling pathway. Clearly, the field of Notch pathway inhibitors is a new and exciting area in cancer research, and additional study of their use both alone and in combination with chemotherapy or other biological agents should be explored.

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