Editorial: gpcr in inflammatory and cancer diseases

Editorial on the Research Topic
GPCR in Inflammatory and Cancer Diseases

The G protein-coupled receptor (GPCR) family represents the largest class of membrane receptors, and displays extensive molecular diversity in terms of response to extracellular stimuli ( 1 ). The GPCRs consequently exhibit pleiotropic activities in human physiology covering cerebral, cardiovascular, digestive, pulmonary, kidney, endocrine and exocrine functions ( 2 ). Notably, they exert a pivotal role in inflammatory processes (i. e., immune cell activity, chemotaxis, angiogenesis, and tissue repair) as well as in the initiation and progression of cancer ( 3 ). Given their structural resolution and drug development, it is estimated that more than 35% of molecules prescribed in human medicine actually target GPCRs ( 4 ). Research during last decade has brought to light the importance of the GPCR family in the treatment of human pathologies associated with the most significant causes of death in the world including chronic inflammatory diseases and many forms of cancer. Very recently, the Covid-19 pandemic has revealed the importance of GPCR network related to the renin-angiotensin system (RAS). In this regard, SARS-CoV-2 infects the human cells via the angiotensin-converting Enzyme 2 (ACE2), an enzyme that normally inactivates angiotensin a GPCR ligand and critical cardiovascular regulator ( 5 7 ). Moreover, Relief Therapeutics is conducting a US Food and Drug Administration (FDA)-approved phase II clinical trial at New York University Langone (NYU Langone Health) to evaluate the use of Aviptadil for Covid-19-related Acute Respiratory Distress Syndrome (ARDS) ( 8 ). Aviptadil is a synthetic form of Human Vasoactive Intestinal Peptide (VIP) which exerts its functions through two GPCR receptors, VPAC1 and VPAC2 as reflected in one of the contributions below ( 8 ).

The present Research Topic assembles six review articles highlighting the importance of GPCRs in human pathological contexts. These articles represent a sample highlighting the relevance of GPCR receptors as attractive targets in the treatment of inflammatory and neurodegenerative diseases but also in cancer. These six review articles emphasize the GPCRs that respond to prototypes of several functional classes of mediators, including neuropeptides (VPAC/PACAP and orexins systems), chemokines (CXCL13 and CXCL12), hormones (melanocortin) and proteases (trypsin, thrombin…), and in the development of new innovative molecules for the treatment of the inflammatory, neurodegenerative diseases, and cancer.

Reviews

2. Couvineau A, Laburthe M. VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins. Br J Pharmacol . (2012) 166: 42–50. doi: 10. 1111/j. 1476-5381. 2011. 01676. x

3. Sun L, Ye RD. Role of G protein-coupled receptors in inflammation. Acta Pharmacol Sin . (2012) 33: 342–50. doi: 10. 1038/aps. 2011. 200

4. Xiao X, Min JL, Wang P, Chou KC. Predict drug-protein interaction in cellular networking. Curr Top Med Chem.(2013) 13: 1707–12. doi: 10. 2174/15680266113139990121

5. Singh Y, Gupta G, Satija S, Pabreja K, Chellappan DK, Dua K. COVID-19 transmission through host cell directed network of GPCR. Drug Dev Res . (2020). 1–5. doi: 10. 1002/ddr. 21674

6. Acconcia F. The network of angiotensin receptors in breast cancer. Cells . (2020) 9: 1336. doi: 10. 3390/cells9061336

7. Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care . (2020) 13: 422. doi: 10. 1186/s13054-020-03120-0

8. https://clinicaltrials. gov/ct2/show/NCT04311697