However, research into the involvement of GPCRs in cancer is directed towards certain GPCR members only.
Current drugs targeting GPCRs have shown excellent therapeutic benefits as GPCRs, like many other kinds of cell surface proteins, can be targetable in several malignancies. There is sufficient evidence that suggests the role of GPCRs in the regulation of the maintenance, differentiation, and pluripotency of cancer stem cells. GPCRs are known to modulate the processes such as proliferative signaling, replicative immortality, evasion of growth suppressors, resistance to apoptosis, initiation of angiogenesis, and activation of invasion and metastasis that are identified as the hallmarks of cancer. Therefore, understanding the molecular relation between GPCRs and malignancies is very important as the pharmacological manipulation of these receptors will become increasingly desirable for the expansion of novel strategies to target tumor progression and metastasis. Finally, GPCRs aid in the creation and preservation of a favorable tumor microenvironment, with effects on nearby blood arteries, signaling molecules, and the extracellular matrix. GPCRs also take part in tumor cell invasion and metastasis by activating Rho GTPases and causing cytoskeletal alterations, as well as angiogenesis, which supplies the cancerous mass with nutrients and provides avenues for metastasis. According to a growing body of research, GPCRs, G proteins, and their downstream signaling targets have now been implicated in cancer initiation and development, where they can affect abnormal cell growth and survival. As a result, GPCR dysregulation is related to a variety of human diseases and disorders, including type 2 diabetes, Alzheimer’s disease, hypertension, and heart failure. GPCRs are the largest and most diverse group of membrane receptors that govern practically all physiological functions through G-protein signaling. Thus, these findings extend the knowledge of GPCRs in cancer cells and help in the identification of therapeutics for cancer patients. This review provides an insight into the various responses mediated by GPCRs in the development of cancers, the molecular mechanisms involved and the novel pharmacological approaches currently preferred for the treatment of cancer. While several studies indicate the role of GPCRs in controlling various aspects of cancer progression such as tumor growth, invasion, migration, survival, and metastasis through its aberrant overexpression, mutations, or increased release of agonists, the explicit mechanisms of the involvement of GPCRs in cancer progression is still puzzling. Integration of these intricate networks of signaling cascades leads to numerous biochemical responses involved in diverse pathophysiological activities, including cancer development. Various molecules such as hormones, lipids, peptides, and neurotransmitters activate GPCRs that enable the coupling of these receptors to highly specialized transducer proteins, called G-proteins, and initiate multiple signaling pathways. G-protein-coupled receptors (GPCRs) are the largest family of cell surface signaling receptors known to play a crucial role in various physiological functions, including tumor growth and metastasis.
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