Splice Variants of G Protein-Coupled Receptors Expressed in Cancers: Effective Targeting with Monoclonal Antibodies and Antibody-Like Scaffolds As Ligands Irrespective of the Pharmacological Status of Isoforms

Abstract

G protein-coupled receptors (GPCRs) form a superfamily of approximately 800–1000 receptors, including cell surface receptors that are internalized with activation and recycled to the plasma membrane. Over 50% of GPCR mRNAs and the open reading frames are comprised of multiple exons, and splice variant isoforms have been identified. These isoforms differ in pharmacological ligand bias, cellular location, and functional outputs. Alternative splicing of mRNAs is a major mechanism in nature to create diversity from single genes and expansion of protein arrays that are tissue specific. Alternative splicing is a dominant phenomenon in tumor transformation, expansion, and survival that generates ne..