{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:25:29Z","timestamp":1789683929718,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In recent years, numerous approaches have been developed to comprehend the molecular alterations underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for the viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumor cells from apoptosis, triggering invasion and metastasis through the enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumor angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as metastatic lesions, exhibit the overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, paracrine, intracrine, and neuroendocrine processes, including the regulation of tumor burden. Consequently, the secretion of SP from TC results in increased SP levels in plasma, which are significantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumor action. They impair cancer cell proliferation on one side and induce apoptosis of tumor cells on the other side. Furthermore, it has been demonstrated that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.<\/jats:p>","DOI":"10.3390\/jcm12196409","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T05:07:13Z","timestamp":1696828033000},"page":"6409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Substance P and Neurokinin-1 Receptor System in Thyroid Cancer: Potential Targets for New Molecular Therapies"],"prefix":"10.3390","volume":"12","author":[{"given":"Inmaculada","family":"Isorna","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-6639","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Gonz\u00e1lez-Moles","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of Granada, 18010 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2853-8481","authenticated-orcid":false,"given":"Miguel","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Research Laboratory on Neuropeptides, Institute of Biomedicine of Seville (IBiS), 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6020-2438","authenticated-orcid":false,"given":"Francisco","family":"Esteban","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain"},{"name":"School of Medicine, University of Seville, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. 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