The challenge of oral squamous cell carcinoma: beyond conventional treatments

Le carcinome épidermoïde buccal (CEB) représente plus de 90 % des cancers de la cavité buccale, avec plus de 350 000 nouveaux diagnostics chaque année à l'échelle mondiale. Malgré les protocoles actuels, le taux de survie à cinq ans reste inférieur à 50 %, et les traitements standards — chirurgie, radiothérapie et chimiothérapie — engendrent une morbidité souvent invalidante pour les patients. L'enjeu clinique majeur réside dans l'identification de molécules à la fois efficaces et moins toxiques.

This scientific review synthesizes recent evidence regarding the use of curcumin and its new formulations in the treatment of oral cancer. The objective is to evaluate how advances in biomedical engineering, such as nanoparticulate vectors, liposomes, and synthetic analogues, make it possible to overcome the compound's historical pharmacokinetic obstacles: low aqueous solubility and limited systemic bioavailability.

The authors explore the hypothesis that these next-generation delivery systems optimize the pro-apoptotic, anti-proliferative, and anti-angiogenic properties of curcumin. The study also examines the potential synergy between these innovative formulations and conventional therapies, aiming to offer a more stable and targeted therapeutic alternative in oral oncology.

Review methodology

This study takes the form of a literature review aiming to synthesize current data on the therapeutic application of curcumin and its advanced formulations in oral oncology. The authors have structured their analysis according to the following parameters:

• Sources and search strategy: A systematic search of PubMed, Scopus, and Web of Science databases was performed for the period from 2000 to 2026.
• Selection criteria: The research targeted in vitro, in vivo studies and clinical trials. Inclusion criteria focused on anticancer mechanisms, targeted delivery systems, pharmacological effects and clinical applications specific to oral squamous cell carcinoma (OSCC).
• Keywords used: Indexing was based on precise terms such as "curcumin", "nanoparticles", "liposomes", "niosomes", "solid lipid nanoparticles", "microemulsions", as well as associated biological processes ("apoptosis", "autophagy", "chemosensitization").
• Data filtering: Publications lacking direct clinical relevance to oral cancer or presenting insufficient methodology were excluded from the analysis by the authors.

Summary of clinical data and mechanisms of action

This literature review highlights the clinical urgency regarding oral squamous cell carcinoma (OSCC), which accounts for more than 90% of oral cancers. The compiled data indicate a global incidence exceeding 350,000 new cases per year, with a stagnant prognosis: the five-year survival rate remains below 50%. The authors point out that 80% of cases are attributable to modifiable risk factors, primarily tobacco and alcohol.

The efficacy of curcumin has been evaluated through several clinical studies and meta-analyses included in this review, particularly for the management of inflammatory pathologies and the side effects of oncological treatments:

On a biological level, the synthesis highlights a therapeutic "double game" of curcumin. In healthy cells, it acts as an antioxidant by neutralizing free radicals and upregulating key enzymes (glutathione peroxidase, catalase, superoxide dismutase) as well as HO-1 and Nrf2 markers. Conversely, in cancer cells, it adopts a pro-oxidant role: it triggers DNA damage and apoptosis by increasing reactive oxygen species (ROS) levels, while sensitizing chemotherapy-resistant cells.

Despite these properties, the authors emphasize that clinical efficacy remains limited by low aqueous solubility and rapid metabolism, leading to subtherapeutic plasma levels even at high oral doses. New vectorization strategies (nanoparticles, liposomes) are presented as necessary solutions to optimize systemic bioavailability.

Analysis of the therapeutic arsenal: from prevention to targeted therapy

Cette revue met en lumière le potentiel de la curcumine dans la gestion du carcinome épidermoïde buccal (CEB), qui représente plus de 90 % des cancers oraux mondiaux. Avec une survie à cinq ans stagnante sous les 50 %, l'intérêt clinique de ce polyphénol réside dans sa dualité biologique : protecteur antioxydant pour les tissus sains et agent pro-oxydant cytotoxique pour les cellules malignes. Les données compilées indiquent que la curcumine induit l'apoptose et inhibe l'angiogenèse tumorale en augmentant les espèces réactives de l'oxygène (ROS), offrant une alternative prometteuse à la morbidité élevée des traitements conventionnels (chirurgie, radiothérapie).

Sur le plan clinique, l'efficacité des formulations topiques est déjà documentée. Les auteurs rapportent qu'un bain de bouche à la curcumine égale la chlorhexidine dans le traitement de la gingivite et réduit significativement l'incidence ainsi que la douleur des mucosites buccales chez les patients irradiés (Amatto et al., 2025). Cependant, l'application systémique pour le CEB reste freinée par une biodisponibilité médiocre et un métabolisme rapide. Les nouvelles stratégies de délivrance — incluant nanoparticules, liposomes et niosomes — cherchent à pallier ces limites en améliorant la solubilité et le ciblage tumoral.

Clinical limits and implications

Le point faible majeur réside dans l'écart entre les résultats précliniques encourageants et la rareté des essais cliniques de phase avancée sur le CEB. Bien que les analogues synthétiques offrent une stabilité accrue, la plupart des preuves d'efficacité anticancer reposent sur des modèles in vitro ou in vivo. Pour le praticien, la curcumine s'impose aujourd'hui comme une option de soutien sécurisée pour la santé muqueuse, tandis que son intégration en tant qu'agent chimiothérapeutique de première intention dépendra de la standardisation de ces vecteurs de nouvelle génération.

Data synthesis

This review reports that oral squamous cell carcinoma (OSCC) accounts for 90% of oral cancers, with a 5-year survival rate of less than 50%. Curcumin exerts a dual action: antioxidant for prevention, it becomes pro-oxidant in malignant cells by triggering apoptosis via the increase of reactive oxygen species (ROS). Clinical data from 2024 and 2025 validate its efficacy in topical application to reduce the severity of radiation-induced mucositis and gingival inflammation.

In concrete terms, for the practitioner:

• Mucositis management: Integrate curcumin-based mouthwashes for your patients undergoing radiotherapy; the 2025 meta-analysis demonstrates a significant reduction in incidence and pain.
• Alternative to chlorhexidine: For the treatment of gingivitis, the 2024 controlled trial indicates that a curcumin formulation is as effective, if not more efficient, in reducing inflammation without the classic adverse effects.
• Exploiting the selective effect: Curcumin offers a safe strategy in oral oncology as it sensitizes resistant cells while protecting healthy tissues through its regulated antioxidant mechanisms (HO-1, Nrf2).

Technical lexicon of the study

Curcumin: A natural polyphenolic compound extracted from the rhizome of Curcuma longa, studied for its extensive pharmacological activities, including its broad-spectrum anti-inflammatory, antioxidant, and anticancer effects.

Carcinome épidermoïde buccal (CEB) : Principale tumeur maligne de la tête et du cou (représentant plus de 90 % des cancers oraux), se développant à partir de l'épithélium squameux tapissant la cavité buccale.

Cellular sensitization: Process by which curcumin improves the efficacy of conventional chemotherapy by increasing the sensitivity of treatment-resistant cancer cells.

Bioavailability: A measure of the amount of substance reaching the systemic circulation. In the case of curcumin, it is limited by rapid metabolic degradation, low aqueous solubility, and marked instability under physiological conditions.

Nanoparticles: Advanced delivery systems used to encapsulate curcumin, improving its solubility, increasing its stability, and promoting targeted release at the tumor site.

Oral mucositis: An inflammatory complication of the oral mucosa frequent in patients undergoing radiotherapy, whose incidence and severity can be reduced by the topical application of curcumin-based formulations.

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