G protein-coupled receptors (GPCRs) are the most common class of therapeutic targets, accounting for ~35% of all FDA-approved drugs. Cancer patients receive numerous medications not only to combat cancer but also to alleviate pain, nausea, and anxiety, many of which target GPCRs. Emerging evidence has implicated GPCRs as drivers of cancer progression, therapeutic resistance, and metastasis. Therefore, the effects of commonly prescribed GPCR-targeted drugs must be reevaluated in the context of cancer. Epidemiological and experimental evidence indicate that widely used GPCR-targeted drugs may promote or inhibit cancer progression. It is crucial that we more fully understand the indirect effects of GPCR-targeted drugs on the cancer phenotype. This review summarizes recent advances in characterizing these interactions and highlights future research opportunities.
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http://dx.doi.org/10.1016/j.tips.2020.10.001 | DOI Listing |
Acta Pharm Sin B
October 2024
Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors.
View Article and Find Full Text PDFJ Ovarian Res
July 2024
Centre of Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanomedicines such as antibody-conjugated drugs and drug-loaded nanoparticles, highlighting a neglected potential to develop personalised treatment. To address the genetic heterogeneity of ovarian cancer, a future personalised approach could include the identification of unique GPCRs expressed in cancer biopsies, matched with personalised GPCR-targeted nanomedicines, for the delivery of lethal drugs to tumour tissue before, during and after surgery.
View Article and Find Full Text PDFTrends Pharmacol Sci
August 2024
Department of Orthopedics and Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address:
Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states.
View Article and Find Full Text PDFFASEB J
July 2024
Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China.
G protein-coupled receptors (GPCRs) are essential contributors to tumor growth and metastasis due to their roles in immune cell regulation. Therefore, GPCRs are potential targets for cancer immunotherapy. Here, we discuss the current understanding of the roles of GPCRs and their signaling pathways in tumor progression from an immunocellular perspective.
View Article and Find Full Text PDFCirc Res
June 2024
Department of Medicine (S.L., P.J.A., S.R., R.J.L., H.A.R.), Duke University Medical Center.
GPCRs (G protein-coupled receptors), also known as 7 transmembrane domain receptors, are the largest receptor family in the human genome, with ≈800 members. GPCRs regulate nearly every aspect of human physiology and disease, thus serving as important drug targets in cardiovascular disease. Sharing a conserved structure comprised of 7 transmembrane α-helices, GPCRs couple to heterotrimeric G-proteins, GPCR kinases, and β-arrestins, promoting downstream signaling through second messengers and other intracellular signaling pathways.
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