GNAS and cancer: Genomic alterations in the components of the GPCR-PKA signaling pathway lead to constitutive activation of this kinase in many human diseases including cancer (Taylor et al., 2013), such as amplified ligands of upstream GPCRs (Coles et al., 2020; McCudden et al., 2005), point mutations in the G-protein subunit GNAS (Patra et al., 2018), inactivation of PKA regulatory protein PKA-RIα (Yin et al., 2011), and mutations that directly alter the activity of the PKA catalytic subunit (PKAc; Berthon et al., 2015).