6. Concluding remarks
GPCR signaling pathways are involved in almost every aspect of
tumorigenesis and progression, including the cancer immune response.
Mutations of GPCRs and G proteins are found in various cancer types.
However, little evidence currently supports a direct link between
specific GPCR or G protein mutations with cancer development, while most
research provide circumstantial evidence that GPCR mutations can act as
weak driver or passenger genes. On one hand, accumulation of GPCR
mutations in some highly conserved structural motifs and the mutually
exclusiveness observed between Gi-coupled GPCR and
GNAS-activating mutations indicate their potential driving role in
cancer. On the other hand, the functional redundancy of GPCR signaling
networks, together with the widespread but low frequency distribution of
GPCR mutations indicate that they are more likely to act as passenger in
cancer development and do not have distinct biological consequences. The
future of GPCR drug discovery for cancer hinges on overcoming challenges
related to data availability and the integration of GPCR research with
broader cancer studies. With regard to this, GPCRomics research aim to
explore and characterize functionally important endogenous GPCRs
associated with health and disease. Through large-scale genomic
analyses, researchers have uncovered novel GPCR mutations and
polymorphisms associated with various cancers, shedding light on
potential biomarkers for early diagnosis and prognosis. As research
progresses, unraveling the complexities of GPCR involvement in cancer
progression will pave the way for more effective and personalized care.