Bombesin Receptor Antibodies

The mammalian bombesin receptor family comprises three class A G protein-coupled receptors, BB₁ (NMBR), BB₂ (GRPR), and BB₃ (BRS3). Neuromedin B and gastrin-releasing peptide preferentially activate BB₁ and BB₂, respectively, whereas BB₃ remains an orphan receptor with no established endogenous ligand. All three subtypes can couple to Gq/11, stimulating phospholipase C and increasing intracellular calcium. BB₁ is expressed in the central nervous system and gastrointestinal tract, while BB₂ is found in the brain, gastrointestinal tract, and pancreas and is overexpressed in subsets of prostate and breast cancers. BB₃ is expressed in brain circuits involved in energy balance, and studies in mice link it to the regulation of food intake, body weight, and glucose homeostasis. Agonist exposure can induce BB₂ desensitization and internalization, with β-arrestins contributing to receptor trafficking. The synthetic BB₃-selective agonist MK-5046 has undergone early clinical testing. BB₂-targeted radioligands have entered clinical studies for tumor imaging and radionuclide therapy, including gallium-68–labeled NeoB for PET and lutetium-177–labeled NeoB for treatment of BB₂-expressing solid tumors. No bombesin receptor-targeted drug is currently approved for therapeutic use.