Old and New Peptide Receptor Targets in Cancer: Future Directions

Abstract

A precise definition of the tumor tissue targets to be selected for in vivo peptide receptor targeting, namely to know which peptide receptor is expressed in which type of cancer, is an important prerequisite for successful clinical application of this technology. In this short review, I give three selected examples of new and promising peptide receptor targets. In the somatostatin receptor field, based on in vitro receptor autoradiography experiments showing that much more sst₂ binding sites are detected in tumors using a ¹⁷⁷Lu-labeled sst₂ antagonist than a ¹⁷⁷Lu-labeled agonist, it can be proposed that, in addition to neuroendocrine tumors, nonneuroendocrine tumors with lower sst₂ levels such as breast carcinomas, renal cell carcinomas, and non-Hodgkin lymphomas may become potential candidates for sst₂ antagonist targeting. In the gastrin-releasing peptide receptor field, recent in vitro data show that not only tumor cells may overexpress gastrin-releasing peptide receptors but also neoangiogenic tumoral vessels, making tumors expressing high levels of gastrin-releasing peptide receptors in tumor vessels, such as ovarian or urinary tract cancers, attractive new candidates for gastrin-releasing peptide receptor targeting. In the incretin receptor field, it was found in vitro that, apart from glucagon-like peptide 1 receptors overexpressed in benign insulinomas, incretin receptors, especially the glucose-dependent insulinotropic polypeptide receptors, can be overexpressed in medullary thyroid cancers, an unexpected finding making also these tumors potential novel candidates for incretin receptor targeting. Due to the abundance of peptide receptors in various cancers, it may be possible in the future to define for each tumor type a corresponding overexpressed peptide receptor suitable for targeting.