Somatostatin analogs: does pharmacology impact antitumor efficacy?

• Novel multireceptor somatostatin analogs may putatively present higher antitumor activities.
• Biased agonism indicates that different somatostatin analogs cannot be considered as simple mimics of the native somatostatins.
• Pharmacologic differences in somatostatin analogs need to be taken into account for optimal use of the somatostatin analogs in the clinic.

Somatostatin is an endogenous inhibitor of secretion and cell proliferation. These features render somatostatin a logical candidate for the management of neuroendocrine tumors that express somatostatin receptors. Synthetic somatostatin analogs (SSAs) have longer half-lives than somatostatin, but have similar activities, and are used for the treatment of these types of disorders. Interest has focused on novel multireceptor analogs with broader affinity to several of the five somatostatin receptors, thereby presenting putatively higher antitumor activities. Recent evidence indicates that SSAs cannot be considered mimics of native somatostatin in regulating signaling pathways downstream of receptors. Here we review this knowledge, discuss the concept of biased agonism, and highlight what considerations need to be taken into account for the optimal clinical use of SSAs.