{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:15:30Z","timestamp":1791688530116,"version":"4.3.4"},"reference-count":80,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005667","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) and Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e Inova\u00e7\u00e3o do Estado de Santa Catarina (FAPESC)","doi-asserted-by":"publisher","award":["2023TR001472"],"award-info":[{"award-number":["2023TR001472"]}],"id":[{"id":"10.13039\/501100005667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005667","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) and Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e Inova\u00e7\u00e3o do Estado de Santa Catarina (FAPESC)","doi-asserted-by":"publisher","award":["2024TR002502"],"award-info":[{"award-number":["2024TR002502"]}],"id":[{"id":"10.13039\/501100005667","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thyroid cancer (TC), the most prevalent endocrine neoplasia, has shown a progressive incidence, highlighting the need for new therapeutic approaches\u2014especially for radioiodine-refractory cases, often associated with mutations in genes such as BRAF, RAS, and TP53. This review proposes a mechanistic model that highlights two interrelated characteristics of the tumor microenvironment (TME): redox imbalance and chronic inflammation, key elements in tumor progression and treatment resistance. Thus, natural phenolic compounds, such as curcumin, quercetin, resveratrol, and epigallocatechin gallate (EGCG), function not as simple antioxidants but as pleiotropic agents that reprogram the TME. A central mechanism of action for these compounds is the modulation of the purinergic axis (CD39\/CD73\/adenosine), a critical immune-metabolic checkpoint. By selectively inducing lethal oxidative stress in tumor cells, suppressing pro-survival inflammatory pathways\u2014such as that mediated by nuclear factor kappa B (NF-\u03baB)\u2014and destabilizing the immunosuppressive shield conferred by adenosine, certain phytochemicals demonstrate the potential to restore immune surveillance and promote tumor apoptosis. In this context, a critical analysis of the evidence related to targeting purinergic signals becomes essential, since pharmacological reinforcement of this pathway, especially when combined with immunotherapies based on immune checkpoint blockade, emerges as a promising strategy for overcoming therapeutic resistance.<\/jats:p>","DOI":"10.3390\/ijms26178474","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting the Purinergic Axis with Phenolic Compounds to Disrupt the Oxidative-Inflammatory Cycle in Thyroid Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1652-9692","authenticated-orcid":false,"given":"J\u00falia Le\u00e3o Batista","family":"Sim\u00f5es","sequence":"first","affiliation":[{"name":"Graduate Program in Biochemistry, Federal University of Santa Catarina (UFSC), Florian\u00f3polis 88040-970, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-4980","authenticated-orcid":false,"given":"Margarete Dulce","family":"Bagatini","sequence":"additional","affiliation":[{"name":"Graduate Program in Biochemistry, Federal University of Santa Catarina (UFSC), Florian\u00f3polis 88040-970, SC, Brazil"},{"name":"Graduate Program in Medical Sciences, Federal University of Fronteira Sul, Chapec\u00f3 89815-899, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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