Head and neck cancer (HNC), which includes epithelial malignancies of the upper aerodigestive tract (oral cavity, oropharynx, pharynx, hypopharynx, larynx, and thyroid), are slowly but consistently increasing, while the overall survival rate remains unsatisfactory. Because of the multifunctional anatomical intricacies of the head and neck, disease progression and therapy-related side effects often severely affect the patient’s appearance and self-image, as well as their ability to breathe, speak, and swallow. Patients with HNC require a multidisciplinary approach involving surgery, radiation therapy, and chemotherapeutics. Chemotherapy is an important part of the comprehensive treatment of tumors, especially advanced HNC, but drug resistance is the main cause of poor clinical efficacy. The most important determinant of this phenomenon is still largely unknown. Recent studies have shown that non-coding RNAs have a crucial role in HNC drug resistance. In addition, they can serve as biomarkers in the diagnosis, treatment, and prognosis of HNCs. In this review, we summarize the relationship between non-coding RNAs and drug resistance of HNC, and discuss their potential clinical application in overcoming HNC chemoresistance.

Background

Head and neck cancer (HNC) is a major global health problem. More than 890,000 new cases of HNC and approximately 450,000 HNC-related deaths occur every year [1,2]. The majority of cases are HN squamous cell carcinoma (HNSCC) [3], involving the stratified epithelium of the oral cavity, pharynx, and larynx, with an overall 5-year survival rate of only 40%–۵۰% [۳]. Most HNC is closely related to tobacco and alcohol use [1–۳]. Patients with HNC might have symptoms including hoarseness, dysphagia, pain, neck mass, and ulcers, which require a multidisciplinary approach involving surgery, radiation therapy, and chemotherapy [4]. Although the treatment is effective for early and locally advanced disease, the prognosis of recurrent and metastatic disease remains poor [5]. Clinically, more than 65% of patients are diagnosed with advanced disease because of the lack of early diagnosis [6]. However, both radiotherapy and surgery reduce patients’ quality of life at this stage [2]. Radiotherapy usually produces obvious side effects, while surgery can significantly affect the normal physiological structure and function of patients [2,7]. Additionally, targeted therapy for HNC has been incorporated into clinical treatment guidelines, but its clinical response and long-term effect are limited, and high costs are associated with this treatment [8]. In recent years, chemical treatment of advanced HNC has been increasingly recognized [9]. In early phase II clinical trials in patients with advanced HNSCC, significant single-agent response rates were up to 30% [5,10].