{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:53:22Z","timestamp":1791572002306,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neural regulation of cancer extends beyond anatomical innervation: tumours receive systemic neural and neuroendocrine inputs and locally produce and decode neurotransmitters and neuropeptides. We propose the Tumour Neurotone (TN) as a tumour-level state of neurochemical regulation generated by the combined actions of these signals across malignant, immune, stromal and vascular compartments, shaping proliferative signalling, metabolic adaptation, immune escape, tissue remodelling, dissemination and treatment response. Biologically, a TN state reflects the context-dependent, spatially organised and relatively persistent configuration of neuroactive ligand availability; cell-type-specific signalling competence, including receptors, transporters and metabolic enzymes; proximal pathway engagement; and downstream cellular responses. TN is therefore not synonymous with tumour innervation, nerve density, an instantaneous neurochemical profile, neuroimmune crosstalk or the broader field of cancer neuroscience; it is a narrower state model intended to capture functional organisation beyond any single neurotransmitter pathway. We synthesise evidence across proliferative signalling, metabolic plasticity, immune regulation, sensory\u2013neuropeptide circuits, neural remodelling, bioelectrical communication, vasculo\u2013stromal organisation and circadian timing. Although many constituent mechanisms are causally supported, the existence and predictive value of integrated TN states have not yet been validated clinically. We therefore specify three criteria for assigning a TN state: temporal reproducibility, predictive value beyond individual components and established tumour covariates, and coherent change after targeted perturbation. We also provide a longitudinal experimental workflow, framework-specific predictions and falsification criteria, and an evidence-graded appraisal of neuromodulatory interventions.<\/jats:p>","DOI":"10.1093\/carcin\/bgag076","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:50:07Z","timestamp":1791460207000},"source":"Crossref","is-referenced-by-count":0,"title":["The Tumour Neurotone: neurochemical regulation of cancer progression and therapy"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-9850","authenticated-orcid":false,"given":"Isaac","family":"Aguirre-Maldonado","sequence":"first","affiliation":[{"name":"Laboratorio de Enfermedades Hep\u00e1ticas, Instituto Nacional de Medicina Gen\u00f3mica , Perif\u00e9rico Sur No. 4809, Col. Arenal Tepepan, Alcald\u00eda Tlalpan, 14610 Ciudad de M\u00e9xico ,","place":["Mexico"]},{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Av. Instituto Polit\u00e9cnico Nacional 2508, 07360 Ciudad de M\u00e9xico ,","place":["Mexico"]},{"name":"Universidad Popular Aut\u00f3noma de Veracruz , Licenciatura en Naturopat\u00eda, Guillermo Prieto No. 8, Col. 2 de Abril, Xalapa, Veracruz 91030 ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josu\u00e9 Jonatan","family":"Pichardo-Espino","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Av. Instituto Polit\u00e9cnico Nacional 2508, 07360 Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Isael","family":"P\u00e9rez-Carre\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Enfermedades Hep\u00e1ticas, Instituto Nacional de Medicina Gen\u00f3mica , Perif\u00e9rico Sur No. 4809, Col. Arenal Tepepan, Alcald\u00eda Tlalpan, 14610 Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Alexander-Aguilera","sequence":"additional","affiliation":[{"name":"Universidad Popular Aut\u00f3noma de Veracruz , Licenciatura en Naturopat\u00eda, Guillermo Prieto No. 8, Col. 2 de Abril, Xalapa, Veracruz 91030 ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Mart\u00ednez-Paez","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico, Facultad de Ciencias, Laboratorio de Biolog\u00eda Molecular , Circuito Exterior s\/n, Circuito de la Investigaci\u00f3n Cient\u00edfica, C.U., 04510 Coyoac\u00e1n, Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Villarruel-Melquiades","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Av. Instituto Polit\u00e9cnico Nacional 2508, 07360 Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"del Pozo-Yauner","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of South Alabama , Mobile, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M","family":"Garc\u00eda-Cuellar","sequence":"additional","affiliation":[{"name":"Subdirecci\u00f3n de Investigaci\u00f3n B\u00e1sica, Instituto Nacional de Cancerolog\u00eda (INCan) , Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesennia","family":"S\u00e1nchez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Subdirecci\u00f3n de Investigaci\u00f3n B\u00e1sica, Instituto Nacional de Cancerolog\u00eda (INCan) , Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Camacho","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Av. Instituto Polit\u00e9cnico Nacional 2508, 07360 Ciudad de M\u00e9xico ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,9]]},"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/carcin\/advance-article-pdf\/doi\/10.1093\/carcin\/bgag076\/71789661\/bgag076.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/advance-article-pdf\/doi\/10.1093\/carcin\/bgag076\/71789661\/bgag076.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:26:55Z","timestamp":1791570415000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/advance-article\/doi\/10.1093\/carcin\/bgag076\/8898803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgag076","relation":{},"ISSN":["0143-3334","1460-2180"],"issn-type":[{"value":"0143-3334","type":"print"},{"value":"1460-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"article-number":"bgag076"}}