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GPCRs initiate complex intracellular signaling networks that regulate vital physiological functions and are associated with numerous diseases, including various types of cancer. Their conserved seven\u2010transmembrane (7TM) structure enables these signaling networks by allowing interactions with multiple ligands and intracellular effectors. In several types of tumors, abnormal GPCR signaling promotes carcinogenesis by supporting immune evasion, cell proliferation, and therapeutic resistance. A significant research gap exists in fully understanding the molecular mechanisms behind pathway\u2010specific activation and biased ligand discovery of GPCRs, which could lead to the development of more effective therapies. This review examines the complexity of GPCRs, with a focus on their role in signaling through the differential activation of pathways regulated by \u03b2\u2010arrestin and G proteins. It discusses how targeted modulation of signaling outcomes by receptor mutants might offer therapeutic benefits in cancer treatment. The review also highlights emerging technologies, such as aptamers, PROTACs, and nanobodies, that more precisely target GPCRs. In addition to exploring receptor structure\u2013function relationships and pathway selectivity, this review provides valuable insights into GPCR\u2010biased signaling and its implications in cancer biology.<\/jats:p>","DOI":"10.1002\/mco2.70375","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T06:50:52Z","timestamp":1758091852000},"source":"Crossref","is-referenced-by-count":13,"title":["G Protein\u2010Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers"],"prefix":"10.1002","volume":"6","author":[{"given":"Inamu Rashid","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Zoology Central University of Kashmir  Ganderbal Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Khurshid","sequence":"additional","affiliation":[{"name":"Watson\u2010Crick Centre for Molecular Medicine Islamic University of Science and Technology  Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Almawash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy Shaqra University  Shaqra Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Biotechnology Shri Mata Vaishno Devi University  Katra Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammira S. 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