Raymond B Penn
Advances in GPCR biology and drug-discovery technology are simultaneously reshaping what can be targeted in asthma and how those strategies must be validated. Recent insights into biased signaling, receptor dimerization and signaling microdomains have revealed new therapeutic opportunities beyond the limitations of traditional β₂-agonist bronchodilation and cytokine-targeted biologics. At the same time, innovations in structural biology, computational modeling, machine learning, biosensor-based pharmacology, and physiologically relevant airway models have transformed the interrogation of GPCRs and the engineering of therapeutics that target them. This review synthesizes these developments, emphasizing how emerging GPCR concepts inform modern discovery platforms, how receptor- and post-receptor signaling control points can be targeted, and how validation across artificial and physiologic systems improves translational fidelity. We further discuss how GPCR therapeutics may reshape clinical development and complement existing biologic therapies in asthma.