GPCR-G protein signalling and its mutational landscape in cancer-Driver or passenger

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• G protein-coupled receptors (GPCRs) are key regulators of cellular signaling pathways.
• Aberrant GPCR expression and mutations are linked to cancer initiation, progression, and immune evasion.
• Understanding the role of GPCRs in cancer is crucial for therapeutic development.

Purpose of the Study:

• To review recent research on the involvement of GPCRs in cancer.
• To evaluate the evidence for GPCR mutations acting as cancer drivers versus passengers.
• To identify challenges and future directions in GPCR-targeted cancer drug discovery.

Main Methods:

• Literature review of recent studies on GPCRs in cancer.
• Analysis of mutation patterns and functional data for GPCRs in various cancers.
• Discussion of signaling network redundancy and mutation frequency distributions.

Main Results:

• Evidence suggests GPCR mutations may act as cancer drivers, indicated by accumulation in conserved motifs and mutual exclusivity with GNAS mutations.
• Conversely, functional redundancy and widespread low-frequency mutations suggest a passenger role for GPCRs.
• The precise role of GPCR mutations in cancer pathogenesis remains complex and context-dependent.

Conclusions:

• GPCRs represent a complex factor in cancer, with mutations potentially acting as drivers or passengers.
• Overcoming data limitations and integrating multi-omics approaches are essential for advancing GPCR-focused cancer research.
• Future drug discovery efforts must address the intricate roles of GPCR signaling networks in oncology.