Development of targeted somatostatin-based antiangiogenic therapy: a review and future perspectives.

Angiogenesis, the development of new blood vessels, is a critical determinant of tumor growth and the dissemination of metastasis. A number of antiangiogenic therapies have been introduced into clinical trials, though few of these are targeted therapies. Somatostatin analogs may be an excellent candidate to develop as targeted antiangiogenic agents alone, or in combination with cytotoxic or cytostatic compounds. Somatostatin analog inhibition of angiogenesis has been demonstrated in the chicken chorioallantoic membrane (CAM) model, the human umbilical vein endothelial cell (HUVEC) proliferation model, and the human placental vein angiogenesis model (HPVAM). This inhibition appears to be the result of a unique upregulation of somatostatin receptor subtype 2 (sst 2) during the angiogenic switch from resting to proliferating endothelium. The distinct overexpression of this receptor provides a unique target for these somatostatin analogs or somatostatin analog conjugates. This manuscript reviews the development of somatostatin analogs as antiangiogenics in both their unlabeled and radiolabeled forms and postulates on future developments in this field.