RESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HNSCC is caused by persistent high-risk human papillomavirus (HR-HPV) infection or excessive consumption of alcohol or tobacco. The persistently low survival rates result from local recurrences and metastases, which are probably caused by so-called tumor stem cells (TSCs). The epithelial-mesenchymal transition (EMT) or transformation is a key event in metastasis initiation and is being increasingly associated with TSCs. OBJECTIVES: This review describes new therapeutic targets in HNSCC, focusing on the TSC hypothesis and EMT regulation. MATERIALS AND METHODS, RESULTS: TSCs and EMT are regulated directly and indirectly via transcription factors and microRNAs (miRNAs). These miRNAs regulate multiple cellular processes and may serve as new therapeutic targets, whose modulation could increase the effectiveness of HNSCC treatments. Post-transcriptionally, miRNAs regulate transcription factors associated with EMT (ZEB1/2, EZH2, Bmi-1), tumor suppressors (p53), TSC markers (ALDH, CD44, EpCAM, p63) and both epithelial (E-cadherin) and mesenchymal markers (vimentin). CONCLUSION: Alterations in HNSSC TSC miRNA expression before and after chemotherapy could potentially serve as a therapeutic control. In the long term, knowledge of a patient's individual protein expression pattern may permit application of specific chemotherapy. Such individualized therapy might prohibit the development of metastases and potentially unresectable recurrences with a high resistance to radiation and chemotherapy, thus improving the prognosis in HNSCC patients.