To grow beyond the size of 2-3 mm3 a tumor needs to arrange its own vasculature in order to supply the tumor cells with their essential nutrients (2-4). Specifically targeting the process of angiogenesis has therefore been a promising strategy for anti-cancer therapies. Even though promising results were obtained in animal tumor models, translating this approach to the clinic has proven to be difficult (5-7). Research has shown that certain tumors are able to shift towards angiogenesis-independent growth upon anti-angiogenesis therapy (8-10). Especially metastases, which are bloodborne and as a consequence generally grow in organs with a high vessel density, are able to target and utilize the existing vascular bed (vessel co-option) and thereby provide access to essential nutrients (8, 11-12). These results suggest that a combination therapy targeting both angiogenesis as well as co-option might prove a more effective treatment strategy.
Interestingly, the cell surface receptor plexin D1 has been shown to be expressed on tumor cells as well as the tumor vasculature in a mouse model of brain metastasis (13). We believe this receptor is a unique candidate for tumor targeting therapies as plexin D1 was shown to be expressed at high levels in the tumor cells as well as its vessels, but not in unaffected brain vessels.
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