Tumor Angiogenesis Unit
New blood vessel formation, or angiogenesis, is a critical hallmark of solid tumor growth and anti-angiogenic agents have become a vital component of current cancer treatment regimens. The appeal of anti-angiogenic therapy can be attributed to several advantages of targeting the endothelial cells that line blood vessels, rather than the tumor cells themselves. First, endothelial cells are directly exposed to circulating blood, facilitating drug delivery and enabling the use of high molecular weight therapeutics. Second, each vessel capillary supports hundreds of tumor cells. Third, endothelial cells are genetically stable and their ability to develop resistance may be limited. Finally, this type of therapy should be applicable to a wide variety of tumor types. Several anti-angiogenic agents that target the vascular endothelial growth factor (VEGF) pathway have been approved for the treatment of cancer. However, tumors can exploit alternative angiogenesis mechanisms when the VEGF pathway is blocked.
A major current goal of our research is to understand the mechanisms of VEGF-independent angiogenesis that can lead to persistent tumor angiogenesis and tumor growth. We are also working to understand the biological functions of several cell surface Tumor Endothelial Markers (TEMs) that were previously found to be elevated in the angiogenic vessels of tumors. Two receptors, TEM5/GPR124 and TEM8/ANTXR1 are of particular interest because of their critical role in angiogenesis. We are using several genetically engineered mouse models to understand the functional role of these TEMs in vivo. We are also developing novel therapeutics, such as TEM8 neutralizing antibodies, in order to block angiogenesis and tumor growth. The end goal of this research is to use new molecular information on tumor angiogenesis to develop clinically useful agents for improved diagnostics and therapeutics of cancer and other vascular diseases.