Tumor subtype-specific receptor targets have revolutionized cancer treatment as they can serve as prognostic, treatment-predictive, and therapeutic targets. Seven transmembrane-domain receptors, also called G protein-coupled receptors (GPCR) constitute the largest family of receptors known, numbering about 900 in human. GPCR have recently started to attract considerable interest in cancer as they are mutated in nearly 20% of human tumors, and many human cancer-associated viruses express constitutively active viral GPCR. As members of this receptor family are currently the most successful targets for clinically useful drugs, GPCR represent a large untapped source of potential targets in cancer treatment. The main focus of our research group is to understand the structure, function, and regulation of GPCR, their pathophysiological roles, and how they can be exploited for prognostic and therapeutic benefit in cancer.
We are especially interested in how these receptors transmit extracellular signals through the plasma membrane to various intracellular effector pathways, how receptors physically interact with one another and with various effectors, how different ligand stimuli for one receptor can select for the activation of specific effectors, translating into functional selectivity, and how receptor-mediated endocytosis regulates the receptor response. The results from these studies are the used to taylor specific ligands for therapeutic benefit.