Head and neck squamous cell carcinoma (HNSCC) develops in the mucosal linings of the upper aerodigestive tract and contributes to approximately 5% of all cancers in the Western world. Well-known risk factors for HNSCC are tobacco smoking, excessive consumption of alcohol and infection with human papillomavirus (HPV). About one third of the patients present with early stage tumours and receive single modality treatment (surgery or radiotherapy). The five-year-survival rate for this patient group is 90%. Unfortunately the majority of patients presents with advanced stages of the disease. These patients are often treated with a combination of surgery and radiotherapy or chemoradiation, the concurrent application of systemic cisplatin chemotherapy and locoregional radiotherapy. Despite major improvements in HNSCC treatment, the long term survival has only moderately improved during the last 20 years. Patients still frequently develop locoregional recurrences, distant metastasis and second primary tumours which results in a five-year-survival rate of less than 60%. Therefore, the development of new anti-cancer agents, which improve patient survival, is most desirable.
Several lines of evidence indicate that head and neck cancers are preceded by preneoplastic fields in the mucosal epithelium characterized by cancer-associated genetic changes. These fields are mostly not visible to the naked eye and remain frequently behind when the tumor is excised or otherwise treated, causing frequent recurrences and second primary tumors (Leemans C. R., et al. 2011). There is at present no treatment for these fields.
Several studies have shown the importance of miRNAs in HNSCC in general. Altered miRNA expression profiles were described in both HNSCC cell lines and tumours when compared to normal controls. A number of miRNAs that had been identified as being differentially expressed were shown to be associated with worse prognosis, such as miR-21 and miR-211. Interestingly, recent studies have described some miRNAs acting as tumour suppressors by targeting certain oncogenes. For example, the miR-16 family has shown antiproliferative effects by negatively regulating cell cycle progression and induction of apoptosis via the silencing of BCL2. Ectopic expression of miR-181a resulted in decreased proliferation via targeting of the oncogene K-RAS. However no new treatment has been yet been developed using a miRNA molecule as active ingredient.
USPTO Backgrounds
USPTO Backgrounds