{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:05:45Z","timestamp":1790067945195,"version":"4.0.1"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Syst. Biol."],"abstract":"<jats:p>Precision oncology has undergone a transformative evolution from static genomic profiling toward dynamic, multi-omics frameworks capable of capturing tumor heterogeneity and adaptive resistance in real time. Central to this paradigm shift is the emerging recognition that G protein-coupled receptors (GPCRs) constitute a vastly underexploited axis of oncogenic signaling, tumor microenvironment (TME) modulation, and non-genetic adaptive resistance. Here we delineate the effective transition to GPCR-focused precision oncology, emphasizing the integrated deployment of next-generation sequencing (NGS), single-cell transcriptomics, expression-based liquid biopsies (ctRNA, exosomal miRNA, circulating tumor cells), and AI-driven quantitative systems network modeling to interrogate GPCR signaling dynamics across solid and hematologic malignancies. GPCRs, comprising approximately 800 human receptors with extensive pharmacological plasticity, encompassing biased agonism, allosteric modulation, receptor heterodimerization, and ligand-independent signaling, serve as critical integrators of extracellular cues and intracellular transcriptional programs. Their overexpression, mutation, and epigenetic dysregulation in multiple cancer types positions them as both prognostic biomarkers and actionable therapeutic targets. We discuss recent advances in integrative genomic platforms, liquid biopsy evolution, case studies of GPCR-driven tumor evolution, and cutting-edge therapeutic modalities, including PROTACs (Proteolysis Targeting Chimeras), biased ligands, RNA therapeutics, and digital twin modeling, to articulate a forward-looking vision for GPCR-centric precision oncology. By harnessing real-time tumor monitoring and AI-optimized adaptive therapies, this framework promises to overcome the limitations of static genomic approaches, enabling mid-treatment recalibration to combat resistance and improve durable survival in heterogeneous solid tumors.<\/jats:p>","DOI":"10.3389\/fsysb.2026.1940022","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:52:03Z","timestamp":1790067123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["GPCR signaling systems facilitate precision interventions for multi-oncology therapy"],"prefix":"10.3389","volume":"6","author":[{"given":"Ashley","family":"Del Pozo","sequence":"first","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Pardo","sequence":"additional","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabitha","family":"Boeringer","sequence":"additional","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter J.","family":"Craig","sequence":"additional","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzia","family":"Sorathia","sequence":"additional","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Millican","sequence":"additional","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Maudsley","sequence":"additional","affiliation":[{"name":"Receptor Biology Lab, Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute","place":["Tampa, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12935-026-04263-w","article-title":"Artificial intelligence-powered liquid biopsy in cancer: a paradigm shift in cancer detection and personalized care","volume":"26","author":"AbdelHamid","year":"2026","journal-title":"Cancer Cell Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"108849","DOI":"10.1016\/j.pharmthera.2025.108849","article-title":"G-protein coupled receptors in metabolic reprogramming and cancer","volume":"270","author":"Ahn","year":"2025","journal-title":"Pharmacol. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.2174\/138945010792006807","article-title":"Tyrosine kinase receptor transactivation associated to G protein-coupled receptors","volume":"11","author":"Almendro","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"B4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s12672-025-02064-7","article-title":"AI-driven biomarker discovery: enhancing precision in cancer diagnosis and prognosis","volume":"16","author":"Alum","year":"2025","journal-title":"Discov. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"100557","DOI":"10.1016\/j.xgen.2024.100557","article-title":"The landscape of cancer-rewired GPCR signaling axes","volume":"4","author":"Arora","year":"2024","journal-title":"Cell Genom"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2002015","DOI":"10.1002\/advs.202002015","article-title":"Mesenchymal transformation: the rosetta stone of glioblastoma pathogenesis and therapy resistance","volume":"7","author":"Azam","year":"2020","journal-title":"Adv. Sci. (Weinh)."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.3390\/ijms17081320","article-title":"G protein-coupled receptors in cancer","volume":"17","author":"Bar-Shavit","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/s41591-020-0880-x","article-title":"BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial","volume":"26","author":"Bockorny","year":"2020","journal-title":"Nat. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.csbj.2025.11.042","article-title":"G protein-coupled receptor digital twins for precision and personalized medicine","volume":"28","author":"Boeringer","year":"2025","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1771718","DOI":"10.3389\/fmolb.2026.1771718","article-title":"GPCR systems coordinate cellular resilience against aging-associated stress","volume":"13","author":"Boeringer","year":"2026","journal-title":"Front. Mol. Biosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"bbaf237","DOI":"10.1093\/bib\/bbaf237","article-title":"Advances and critical aspects in cancer treatment development using digital twins","volume":"26","author":"Bouriga","year":"2025","journal-title":"Brief. Bioinform"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1073\/pnas.1701529114","article-title":"Distinct conformations of GPCR-\u03b2-arrestin complexes mediate desensitization, signaling, and endocytosis","volume":"114","author":"Cahill","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e70539","DOI":"10.1002\/cnr2.70539","article-title":"Clinical significance of biomarkers in oropharyngeal squamous cell carcinoma: recurrence prediction and treatment response","volume":"9","author":"Chen","year":"2026","journal-title":"Cancer Rep. Hob."},{"key":"B14","doi-asserted-by":"publisher","first-page":"6337","DOI":"10.7150\/thno.99025","article-title":"PET imaging of CXCR4 expression using [18F]AlF-NOTA-QHY-04 for hematologic malignancy and solid tumors","volume":"14","author":"Cheng","year":"2024","journal-title":"Theranostics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s44368-026-00019-w","article-title":"Engineering microbial metabolites to modulate tumor immunity and advance cancer immunotherapy","volume":"3","author":"Chigozie","year":"2026","journal-title":"Discov. Immun."},{"key":"B16","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/s00432-024-05816-0","article-title":"Spatial transcriptomics in cancer research and potential clinical impact: a narrative review","volume":"150","author":"Cilento","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.46439\/cancerbiology.5.066","article-title":"Proton sensing GPCR's: the missing link to Warburg's oncogenic legacy?","volume":"5","author":"Cornell","year":"2024","journal-title":"J. Cancer Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3390\/cimb48020127","article-title":"GPCR-mediated cell intelligence: a potential mechanism for survival and long-term health","volume":"48","author":"Craig","year":"2026","journal-title":"Curr. Issues Mol. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"863","DOI":"10.3390\/biom12070863","article-title":"What makes GPCRs from different families bind to the same ligand?","volume":"12","author":"Dankwah","year":"2022","journal-title":"Biomolecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s10549-020-05817-w","article-title":"Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer","volume":"184","author":"Diamond","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"B21","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00262-024-03801-7","article-title":"GPCRs: emerging targets for novel T cell immune checkpoint therapy","volume":"73","author":"Dickinson","year":"2024","journal-title":"Cancer Immunol. Immunother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"216280","DOI":"10.1016\/j.canlet.2023.216280","article-title":"A complex of wnt\/Planar cell polarity signaling components Vangl1 and Fzd7 drives glioblastoma multiforme malignant properties","volume":"567","author":"Dreyer","year":"2023","journal-title":"Cancer Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41392-024-01760-0","article-title":"New clinical trial design in precision medicine: discovery, development and direction","volume":"9","author":"Duan","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"C887","DOI":"10.1152\/ajpcell.00449.2021","article-title":"GPCR systems pharmacology: a different perspective on the development of biased therapeutics","volume":"322","author":"Eiger","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.3390\/cells1511103","article-title":"Artificial intelligence in tumor evolution: understanding cancer complexity through multi-modal data integration in precision oncology","volume":"15","author":"Espinosa-S\u00e1nchez","year":"2026","journal-title":"Cells"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5686","DOI":"10.1158\/1078-0432.CCR-18-3382","article-title":"HDAC inhibition enhances the in vivo efficacy of MEK inhibitor therapy in uveal melanoma","volume":"25","author":"Fai\u00e3o-Flores","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3390\/biom16020325","article-title":"Targeted protein degradation in cancer: protacs, new targets, and clinical mechanisms","volume":"16","author":"Faryal","year":"2026","journal-title":"Biomolecules"},{"key":"B28","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.urolonc.2024.07.001","article-title":"A global view of the challenges and limitations of precision medicine for genitourinary cancers","volume":"42","author":"Fontes","year":"2024","journal-title":"Urol. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"102703","DOI":"10.1016\/j.ctrv.2024.102703","article-title":"Tumor-agnostic baskets to N-of-1 platform trials and real-world data: transforming precision oncology clinical trial design","volume":"125","author":"Fountzilas","year":"2024","journal-title":"Cancer Treat. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.1440-1827.2010.02548.x","article-title":"CXCR4 and cancer","volume":"60","author":"Furusato","year":"2010","journal-title":"Pathol. Int."},{"key":"B31","doi-asserted-by":"publisher","first-page":"841890","DOI":"10.3389\/fonc.2022.841890","article-title":"Multi-omics analysis of glioblastoma and glioblastoma cell line: molecular insights into the functional role of GPR56 and TG2 in mesenchymal transition","volume":"12","author":"Ganesh","year":"2022","journal-title":"Front. Oncol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jncc.2026.01.006","article-title":"Adaptive therapy: a balanced triangle for chronic cancer management","volume":"6","author":"Guan","year":"2026","journal-title":"J. Natl. Cancer Cent."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e5768926","DOI":"10.1155\/jimr\/5768926","article-title":"A hidden checkpoint: bidirectional pH remodeling of the immunological synapse in cancer, methods, and therapeutic opportunities","volume":"2026","author":"Guillemette","year":"2026","journal-title":"J. Immunol. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1200\/JCO-25-01983","article-title":"Precision oncology 2.0: guiding magic bullets with expression-based liquid biopsy","volume":"44","author":"Gulati","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"991","DOI":"10.4143\/crt.2024.128","article-title":"Precision oncology clinical trials: a systematic review of phase II clinical trials with biomarker-driven, adaptive design","volume":"56","author":"Ha","year":"2024","journal-title":"Cancer Res. Treat."},{"key":"B36","doi-asserted-by":"publisher","first-page":"115921","DOI":"10.1016\/j.bcp.2023.115921","article-title":"The development of potent, competitive CXCR4 antagonists for the prevention of cancer metastasis","volume":"218","author":"Hamshaw","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1579922","DOI":"10.3389\/fdsfr.2025.1579922","article-title":"Federated learning: a privacy-preserving approach to data-centric regulatory cooperation","volume":"5","author":"Horst","year":"2025","journal-title":"Front. Drug Saf. Regul."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e34","DOI":"10.1016\/S1470-2045(24)00395-4","article-title":"Advances and challenges in precision imaging","volume":"26","author":"Hricak","year":"2025","journal-title":"Lancet Oncol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s10238-025-01965-9","article-title":"AI-driven multi-omics integration in precision oncology: bridging the data deluge to clinical decisions","volume":"26","author":"Hsu","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"bbaf566","DOI":"10.1093\/bib\/bbaf566","article-title":"Single-cell multi-omics and machine learning for dissecting stemness in cancer","volume":"26","author":"Huang","year":"2025","journal-title":"Brief. Bioinform"},{"key":"B41","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3389\/fgene.2016.00056","article-title":"Exosomes: the link between GPCR activation and metastatic potential?","volume":"7","author":"Isola","year":"2016","journal-title":"Front. Genet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13040-025-00442-z","article-title":"Network-based multi-omics integrative analysis methods in drug discovery: a systematic review","volume":"18","author":"Jiang","year":"2025","journal-title":"BioData Min."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1349097","DOI":"10.3389\/fphar.2024.1349097","article-title":"Orphan G protein-coupled receptors: the ongoing search for a home","volume":"15","author":"Jobe","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3390\/cimb47030189","article-title":"Unravelling convergent signaling mechanisms underlying the aging-disease nexus using computational language analysis","volume":"47","author":"Junyent","year":"2025","journal-title":"Curr. Issues Mol. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"13117","DOI":"10.1073\/pnas.2000430117","article-title":"DCyFIR: a high-throughput CRISPR platform for multiplexed G protein-coupled receptor profiling and ligand discovery","volume":"117","author":"Kapolka","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e70375","DOI":"10.1002\/mco2.70375","article-title":"G protein-coupled receptor signaling: implications and therapeutic development advances in cancers","volume":"6","author":"Khan","year":"2020","journal-title":"MedComm"},{"key":"B47","doi-asserted-by":"publisher","first-page":"3603","DOI":"10.1016\/j.cell.2025.03.046","article-title":"Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network","volume":"188","author":"Kleist","year":"2025","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s44386-025-00011-8","article-title":"Intracellular GPCR modulators enable precision pharmacology","volume":"2","author":"Krumm","year":"2025","journal-title":"NPJ Drug Discov."},{"key":"B49","doi-asserted-by":"publisher","first-page":"6655417","DOI":"10.1155\/2021\/6655417","article-title":"Unraveling the molecular nexus between GPCRs, ERS, and EMT","volume":"2021","author":"Kumari","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"B50","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/aps.2011.18","article-title":"GPCRs and cancer","volume":"33","author":"Lappano","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"B51","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s12943-025-02426-3","article-title":"Single-cell multi-omics in cancer immunotherapy: from tumor heterogeneity to personalized precision treatment","volume":"24","author":"Le","year":"2025","journal-title":"Mol. Cancer"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.3390\/ijms19102919","article-title":"G protein-coupled receptor systems as crucial regulators of DNA damage response processes","volume":"19","author":"Leysen","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"13387","DOI":"10.3390\/ijms222413387","article-title":"GPCRs are optimal regulators of complex biological systems and orchestrate the interface between health and disease","volume":"22","author":"Leysen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"997664","DOI":"10.3389\/fphar.2022.997664","article-title":"Therapeutic and prognostic potential of GPCRs in prostate cancer from multi-omics landscape","volume":"13","author":"Li","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"106988","DOI":"10.1016\/j.compbiomed.2023.106988","article-title":"Multi-omics integration analysis of GPCRs in pan-cancer to uncover inter-omics relationships and potential driver genes","volume":"161","author":"Li","year":"2023","journal-title":"Comput. Biol. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1795789","DOI":"10.3389\/fimmu.2026.1795789","article-title":"Liquid biopsy in cancer drug resistance: real-time monitoring, mechanistic insights, and translational applications","volume":"17","author":"Li","year":"2026","journal-title":"Front. Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.21037\/tlcr-23-739","article-title":"GPRC5A is a potential prognostic biomarker and correlates with immune cell infiltration in non-small cell lung cancer","volume":"13","author":"Lin","year":"2024","journal-title":"Transl. Lung Cancer Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1186\/s13046-019-1370-1","article-title":"miR-504 suppresses mesenchymal phenotype of glioblastoma by directly targeting the FZD7-mediated Wnt-\u03b2-catenin pathway","volume":"38","author":"Liu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e17188","DOI":"10.1002\/advs.202517188","article-title":"GPCRs in CAR-T cell immunotherapy: expanding the target landscape and enhancing therapeutic efficacy","volume":"13","author":"Liu","year":"2025","journal-title":"Adv. Sci. (Weinh)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41392-026-02631-6","article-title":"Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications","volume":"11","author":"Liu","year":"2026","journal-title":"Signal Transduct. Target Ther."},{"key":"B61","doi-asserted-by":"publisher","first-page":"480","DOI":"10.3390\/ph19030480","article-title":"AI-Driven design of miniproteins as potential allosteric modulators","volume":"19","author":"Liu","year":"","journal-title":"Pharm. (Basel)."},{"key":"B62","doi-asserted-by":"publisher","first-page":"3002","DOI":"10.3390\/cancers13123002","article-title":"From sampling to sequencing: a liquid biopsy pre-analytic workflow to maximize multi-layer genomic information from a single tube","volume":"13","author":"Maass","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B63","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1056\/NEJMoa0800668","article-title":"Detection of mutations in EGFR in circulating lung-cancer cells","volume":"359","author":"Maheswaran","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1002\/1878-0261.13707","article-title":"Precision cancer medicine 2.0\u2014oncology in the postgenomic era","volume":"18","author":"Masina","year":"2024","journal-title":"Mol. Oncol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.jalz.2018.01.014","article-title":"Intelligent and effective informatic deconvolution of \u201cBig Data\u201d and its future impact on the quantitative nature of neurodegenerative disease therapy","volume":"14","author":"Maudsley","year":"2018","journal-title":"Alzheimers Dement."},{"key":"B66","first-page":"725","article-title":"Systems pharmacology: enabling multidimensional therapeutics","volume-title":"Reference Module in Biomedical Sciences, Comprehensive Pharmacology","author":"Maudsley","year":"2022"},{"key":"B67","doi-asserted-by":"publisher","first-page":"13598","DOI":"10.3390\/ijms232113598","article-title":"Intersection of the orphan G protein-coupled receptor, GPR19, with the aging process","volume":"23","author":"Maudsley","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/nchembio.2527","article-title":"Structure-inspired design of \u03b2-arrestin-biased ligands for aminergic GPCRs","volume":"14","author":"McCorvy","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.3390\/microorganisms8101504","article-title":"G protein-coupled receptor genes, PTGDR1, PTGDR2, and PTGIR, are candidate epigenetic biomarkers and predictors for treated patients with HPV-Associated oropharyngeal cancer","volume":"8","author":"Misawa","year":"2020","journal-title":"Microorganisms"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1794130","DOI":"10.3389\/fimmu.2026.1794130","article-title":"Multidimensional tumor heterogeneity and its role in therapeutic resistance","volume":"17","author":"Mubin","year":"2026","journal-title":"Front. Immunol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/bcp.14611","article-title":"Exosomes and extracellular vesicles as liquid biopsy biomarkers in diffuse large B-cell lymphoma: current state of the art and unmet clinical needs","volume":"87","author":"Ofori","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"12690","DOI":"10.3390\/ijms241612690","article-title":"Omics technologies improving breast cancer research and diagnostics","volume":"24","author":"Orsini","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41698-024-00583-0","article-title":"Overcoming limitations in current measures of drug response May enable AI-driven precision oncology","volume":"8","author":"Ovchinnikova","year":"2024","journal-title":"NPJ Precis. Oncol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"3211","DOI":"10.1093\/bioinformatics\/btt565","article-title":"GPCR ontology: development and application of a G protein-coupled receptor pharmacology knowledge framework","volume":"29","author":"Przydzial","year":"2013","journal-title":"Bioinformatics"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1765361","DOI":"10.3389\/fimmu.2026.1765361","article-title":"Immunomodulatory crosstalk between GPCR and hippo signaling in cancer: implications for tumor immunity and therapeutic targeting","volume":"17","author":"Ren","year":"2026","journal-title":"Front. Immunol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41746-020-00323-1","article-title":"The future of digital health with federated learning","volume":"3","author":"Rieke","year":"2020","journal-title":"NPJ Digit. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1007\/s12032-025-02817-y","article-title":"Precision oncology: transforming cancer care through personalized medicine","volume":"42","author":"Rituraj","year":"2025","journal-title":"Med. Oncol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13041-026-01319-w","article-title":"Leveraging single-cell and spatial omics for brain tumour insights to improve therapeutic strategies","volume":"19","author":"Roy","year":"2026","journal-title":"Mol. Brain."},{"key":"B79","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/17460441.2025.2450636","article-title":"Advances in cryo-electron microscopy (cryoEM) for structure-based drug discovery","volume":"20","author":"Rubach","year":"2025","journal-title":"Expert Opin. Drug Discov."},{"key":"B80","doi-asserted-by":"publisher","first-page":"100013","DOI":"10.1016\/j.molpha.2024.100013","article-title":"G protein-coupled receptor-targeted proteolysis-targeting chimeras in cancer therapeutics","volume":"107","author":"Saca","year":"2025","journal-title":"Mol. Pharmacol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"100560","DOI":"10.1016\/j.xgen.2024.100560","article-title":"Exploring GPCR signaling pathway networks as cancer therapeutic targets","volume":"4","author":"Santhanam","year":"2024","journal-title":"Cell Genom"},{"key":"B82","doi-asserted-by":"publisher","first-page":"2450412","DOI":"10.1080\/17441692.2025.2450412","article-title":"Addressing challenges in the implementation of precision oncology: an in-depth examination of limitations and disparities in the treatment of NSCLC in the Brazilian public healthcare system (SUS)","volume":"20","author":"Schneider","year":"2025","journal-title":"Glob. Public Health"},{"key":"B83","doi-asserted-by":"publisher","first-page":"oyaf152","DOI":"10.1093\/oncolo\/oyaf152","article-title":"The present and future of precision oncology and tumor-agnostic therapeutic approaches","volume":"30","author":"Shah","year":"2025","journal-title":"Oncologist"},{"key":"B84","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/s40001-023-01346-6","article-title":"Prediction of survival and immunotherapy response by the combined classifier of G protein-coupled receptors and tumor microenvironment in melanoma","volume":"28","author":"Shen","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jb\/mvae029","article-title":"Cryo-EM advances in GPCR structure determination","volume":"176","author":"Shihoya","year":"2024","journal-title":"J. Biochem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/s42003-026-09516-y","article-title":"Strategic advances for cryo-EM structural studies of small (<100 kDa) GPCRs","volume":"9","author":"Singh","year":"2026","journal-title":"Commun. Biol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"e3000434","DOI":"10.1371\/journal.pbio.3000434","article-title":"GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors","volume":"17","author":"Sriram","year":"2019","journal-title":"PLoS Biol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1146\/annurev-pharmtox-061724-080852","article-title":"Targeting G protein-coupled receptors in immuno-oncological therapies","volume":"65","author":"Stagg","year":"2025","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3390\/cancers18010140","article-title":"Liquid biopsy in cancer: the importance of integrating bioinformatics approaches towards the development of a personalized molecular profile","volume":"18","author":"Strati","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B90","doi-asserted-by":"publisher","first-page":"108616","DOI":"10.1016\/j.bioorg.2025.108616","article-title":"G-protein-coupled receptor FZD7 as a therapeutic target in glioblastoma: multi-cohort validation and identification of cycloartobiloxanthone as an inhibitor","volume":"162","author":"Sun","year":"2025","journal-title":"Bioorg. Chem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.chembiol.2025.07.006","article-title":"Inhibiting cancer metastasis with water-solubilized membrane receptor CXCR4QTY-Fc as a molecular trap","volume":"32","author":"Sun","year":"","journal-title":"Cell Chem. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.trecan.2024.06.009","article-title":"Precision oncology: current and future platforms for treatment selection","volume":"10","author":"Tang","year":"2024","journal-title":"Trends Cancer"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.3389\/fphar.2018.01369","article-title":"\u03b2-Arrestin based receptor signaling paradigms: potential therapeutic targets for complex age-related disorders","volume":"9","author":"van Gastel","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.cmet.2025.10.011","article-title":"From microbiome to metabolism: bridging a two-decade translational gap","volume":"38","author":"Van Hul","year":"2026","journal-title":"Cell Metab."},{"key":"B95","doi-asserted-by":"publisher","first-page":"ed86","DOI":"10.3332\/ecancer.2018.ed86","article-title":"Precision oncology: as much expectations as limitations","volume":"12","author":"Vasconcellos","year":"2018","journal-title":"Ecancermedicalscience"},{"key":"B96","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13059-024-03293-9","article-title":"TMO-Net: an explainable pretrained multi-omics model for multi-task learning in oncology","volume":"25","author":"Wang","year":"2024","journal-title":"Genome Biol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1603950","DOI":"10.3389\/fphar.2025.1603950","article-title":"Progress in structure-based drug development targeting chemokine receptors","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"801","DOI":"10.3390\/cancers17050801","article-title":"Tumor-agnostic therapies in practice: challenges, innovations, and future perspectives","volume":"17","author":"Wu","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B99","doi-asserted-by":"publisher","first-page":"11062","DOI":"10.1074\/jbc.REV119.005601","article-title":"Illuminating the Onco-GPCRome: novel G protein-coupled receptor-driven oncocrine networks and targets for cancer immunotherapy","volume":"294","author":"Wu","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/s41590-023-01529-7","article-title":"The GPCR-G\u03b1s-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure","volume":"24","author":"Wu","year":"2023","journal-title":"Nat. Immunol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"776","DOI":"10.7150\/jca.90990","article-title":"Multi-omics identification of GPCR gene features in lung adenocarcinoma based on multiple machine learning combinations","volume":"15","author":"Xie","year":"2024","journal-title":"J. Cancer"},{"key":"B102","doi-asserted-by":"publisher","first-page":"6576","DOI":"10.7150\/thno.130266","article-title":"The CXCR4-targeted theranostics era: a comprehensive review of a decade of progress (2015-2025)","volume":"16","author":"Yang","year":"2026","journal-title":"Theranostics"},{"key":"B103","doi-asserted-by":"publisher","first-page":"e20634","DOI":"10.1002\/advs.202520634","article-title":"T cell exhaustion in cancer immunotherapy: heterogeneity, mechanisms, and therapeutic opportunities","volume":"13","author":"Yu","year":"2026","journal-title":"Adv. Sci. (Weinh)"},{"key":"B104","doi-asserted-by":"publisher","first-page":"102195","DOI":"10.1016\/j.omtn.2024.102195","article-title":"RNA therapeutics in targeting G protein-coupled receptors: recent advances and challenges","volume":"35","author":"Yuan","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B105","doi-asserted-by":"publisher","first-page":"4496","DOI":"10.7150\/ijbs.127859","article-title":"Activation of GABBR1 by new ligand valerate transcriptionally regulates ATF4-NRF2-CXCL13 axis mediating CD8+ T cell anti-tumor immunity","volume":"22","author":"Zhai","year":"2026","journal-title":"Int. J. Biol. Sci."},{"key":"B106","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41392-024-01803-6","article-title":"G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"B107","doi-asserted-by":"publisher","first-page":"9950","DOI":"10.1038\/s41467-024-54251-9","article-title":"GPRC5A promotes lung colonization of esophageal squamous cell carcinoma","volume":"15","author":"Zhou","year":"2024","journal-title":"Nat. Commun."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1080\/10543406.2025.2489292","article-title":"An improved biomarker-guided adaptive patient enrichment design for oncology trials","volume":"35","author":"Zhou","year":"2025","journal-title":"J. Biopharm. Stat."},{"key":"B109","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/164_2025_771","article-title":"Biased allosteric modulation in GPCR drug discovery","volume":"290","author":"Zhou","year":"2026","journal-title":"Handb. Exp. Pharmacol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.21037\/atm-21-1948","article-title":"A narrative review of tumor heterogeneity and challenges to tumor drug therapy","volume":"9","author":"Zhu","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"B111","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/s41419-026-08795-x","article-title":"Multi-omics reveals CXCR4 drives immune escape in colorectal cancer via metabolic reprogramming and immune microenvironment remodeling","volume":"17","author":"Zhu","year":"2026","journal-title":"Cell Death Dis."}],"container-title":["Frontiers in Systems Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsysb.2026.1940022\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:52:05Z","timestamp":1790067125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsysb.2026.1940022\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":111,"alternative-id":["10.3389\/fsysb.2026.1940022"],"URL":"https:\/\/doi.org\/10.3389\/fsysb.2026.1940022","relation":{},"ISSN":["2674-0702"],"issn-type":[{"value":"2674-0702","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1940022"}}