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.