Molecular targeting of Gα and Gβγ subunits: a potential approach for cancer therapeutics

G-Protein-coupled receptors (GPCRs) signal through G protein alpha and beta gamma subunit families to regulate a wide range of physiological and pathophysiological processes. As such, GPCRs are major targets for therapeutic drugs. Downstream targets of GPCRs have also gained interest as a therapeutic approach to complex pathologies involving multiple GPCRs. One such approach involves targeting of the G proteins themselves. Several small molecule G alpha and G beta gamma modulators have been developed and been tested in various animal models of disease. Here we will discuss the requirements for targeting G alpha and G beta gamma subunits, the mechanisms of action of currently identified inhibitors, and focus on the potential utility of G alpha and G beta gamma inhibitors in the treatment of various cancers.