{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:20:03Z","timestamp":1791652803196,"version":"4.3.4"},"reference-count":332,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006742","name":"CESPU\u2014Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio Crl","doi-asserted-by":"publisher","award":["DNAOralCan-GI2-CESPU-2025"],"award-info":[{"award-number":["DNAOralCan-GI2-CESPU-2025"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006742","name":"CESPU\u2014Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio Crl","doi-asserted-by":"publisher","award":["TargetMito-GI2-CESPU-2025"],"award-info":[{"award-number":["TargetMito-GI2-CESPU-2025"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DNAOralCan-GI2-CESPU-2025"],"award-info":[{"award-number":["DNAOralCan-GI2-CESPU-2025"]}],"id":[{"id":"https:\/\/ror.org\/00w7bj245","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TargetMito-GI2-CESPU-2025"],"award-info":[{"award-number":["TargetMito-GI2-CESPU-2025"]}],"id":[{"id":"https:\/\/ror.org\/00w7bj245","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with particular emphasis on oral cancer. We integrate the available evidence to assess the biological rationale, therapeutic potential, and current limitations of curcumin-based approaches. The molecular mechanisms underlying their antitumor activity are discussed, including modulation of EGFR\/ERK and PI3K\/Akt signaling pathways, inhibition of NF-\u03baB and STAT3 activation, induction of apoptosis, regulation of oxidative stress, and suppression of epithelial\u2013mesenchymal transition and tumor invasiveness. In addition, we address the impact of curcumin on the tumor microenvironment and its role in overcoming intrinsic cellular resistance mechanisms. The review also highlights advances in drug delivery strategies, such as nanoformulations, that are designed to improve curcumin\u2019s bioavailability and therapeutic efficacy. By critically integrating current evidence, this review highlights both the promise and the challenges associated with curcumin-based monotherapy in HNC, emphasizing the need for more robust and clinically relevant studies to support future translation.<\/jats:p>","DOI":"10.3390\/ijms27125626","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1272-0186","authenticated-orcid":false,"given":"Luana","family":"Pinto","sequence":"first","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-4286","authenticated-orcid":false,"given":"Jo\u00e3o P. N.","family":"Silva","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-1297","authenticated-orcid":false,"given":"Lu\u00eds","family":"Monteiro","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-7321","authenticated-orcid":false,"given":"Patr\u00edcia M. A.","family":"Silva","sequence":"additional","affiliation":[{"name":"UNIPRO-Oral Pathology and Rehabilitation Research Unit, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, 1H-TOXRUN, IUCS-CESPU, University Institute of Health Sciences, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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