Molecularly targeted therapies in head and neck cancers

Head and neck cancers (HNC) are 6th most common malignancies according to the incidence rate. Over 85% of tumors of this region are epithelial tumors, especially squamous cell carcinomas (head and neck squamous cell carcinomas - HNSCC). Surgery, chemotherapy and radiotherapy are still the standard for the treatment of HNC. Despite the great development of the various methods of treatment, survival of patients have not improved significantly over the last 30 years, with the overall, 5-year survival not exceeding 50%. Progress in understanding the biology of cancer leads to personalization of therapy and introduction of drugs with molecular mechanism of action to everyday practice. At present, the effectiveness of monoclonal antibodies against EGFR in the treatment of HNSCC has already been proven. Cetuximab in combination with radiotherapy was found to be effective in patients with advanced and locally advanced HNSCC. There are also some promising results of phase III trials with zalutumumab and panitumumab. Initial efficacy of sorafenib (an inhibitor of the intracellular domain of VEGFR, PDGFR and c-Kit) and afatinib (an irreversible inhibitor of pan-HER tyrosine kinase) have been demonstrated. Great hopes for the future are linked with the potential use of STAT3, EGFRvIII, abnormal proteins K-ras, H-ras and PTEN as well as proteasome as a target for therapy.