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Most tumors stimulate production of new blood vessels, which, in turn, sustain the growing number of tumor cells. For this reason, angiogenesis inhibitors are used in cancer therapy; however, many tumors develop resistance to currently available angiogenesis inhibitors.
A team from California and Michigan reported that a microRNA called miR-132 enhances the ability of endothelial cells to form tubes that become new vessels. miR-132 was found at high levels in the endothelium of human tumors and hemangiomas, but it was not detected in normal endothelium. Administering another small RNA that attenuated production of miR-132 greatly inhibited angiogenesis in mice. The team then created nanoparticles that contained this miR-132 inhibitor. These nanoparticles targeted endothelial cells by attaching to a specific molecule on their surface; the nanoparticles prevented angiogenesis and lowered tumor burden in a mouse model of human breast cancer.
Anand S et al. MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med 2010 Aug; 16:909. (http://dx.doi.org/10.1038/nm.2186)
Comment
Small-molecule therapies have many advantages over protein therapies, such as current angiogenesis inhibitors. If miR-132 is essential for angiogenesis, then small-molecule antagonists of miR-132 might prove to be a new form of cancer therapy. Angiogenesis also plays a role in non-neoplastic diseases, such as macular degeneration; thus, antagonists of miR-132 might have broader application, as well.