* Correspondence: l.h.heitman@lacdr.leidenuniv.nl
Abstract: G protein-coupled receptors (GPCRs) play a crucial
role in cellular signaling, regulating various physiological processes.
Abnormal expression and mutations of GPCRs have been implicated in
several types of cancer, influencing tumor initiation, progression, and
immune response. In this review, we present an overview of recent
research on GPCR involvement in cancer, and discuss the evidence
supporting whether mutations in GPCRs act as cancer driver or passenger.
Accumulation of GPCR mutations in some highly conserved structural
motifs and the mutually exclusiveness observed between
Gi-coupled GPCRs and GNAS-activating mutations indicate
their potential driving role in cancer. However, the functional
redundancy of GPCR signaling networks, together with the widespread but
low frequency distribution of GPCR mutations indicate that they may
rather act as passengers. The future of GPCR drug discovery hinges on
overcoming challenges related to data availability and the integration
of GPCR research with broader cancer studies using multi-omics
approaches.
KeywordsG protein-coupled receptor (GPCR), cancer, driver mutation, passenger
mutation, cellular signaling