Mechanisms and therapeutic applications of curcumin and its derivatives in head-and-neck squamous cell carcinoma

Primary head-and-neck squamous cell carcinoma (HNSCC) is a significant global health concern, strongly associated with smoking, alcohol consumption, human papillomavirus infection (particularly in oropharyngeal cancer), and carcinogen exposure. The term “head-and-neck cancer” broadly encompasses malignancies of the head-and-neck region, including nasopharyngeal and oral cancers. Due to its complex anatomy and occult nature, most patients are diagnosed at an advanced local stage (Stage III/IV). Treatment frequently results in recurrence and metastasis, leading to poor 5-year survival rates. Curcumin, an extract from traditional Chinese medicine, exhibits anti-inflammatory, antioxidant, and multitargeted anticancer activities. Compared to conventional formulations, curcumin derivatives demonstrate enhanced stability, solubility, and pharmacokinetics, offering therapeutic potential in HNSCC. This review highlights recent advancements in the antitumor mechanisms of curcumin and its derivatives in primary HNSCC. The objective is to provide innovative insights that could inform the development of more comprehensive and effective treatment strategies for HNSCC. A comprehensive search of the PubMed database was conducted using advanced filters and Boolean logic with relevant Medical Subject Headings terms and keywords, covering publications from 1987 to April 17, 2025. After screening titles and abstracts, 272 publications were selected, including 158 published in the last decade and 85 within the past 5 years. Curcumin and its derivatives demonstrate antitumor properties by disrupting the cell cycle, inducing apoptosis, modulating key signaling pathways, inhibiting invasion and metastasis, regulating epigenetic activities, and inducing oxidative stress and autophagy. They also show synergy with radiochemotherapy, immunotherapy, and photodynamic therapy. Their multifaceted antitumor properties and favorable safety profiles underscore their potential as effective adjuvant therapies in the treatment of HNSCC.