From novel insights in molecular biology to targeted treatment approaches in head and neck cancer

Squamous-cell carcinoma of the head and neck is the fifth commonest neoplasm worldwide.Over 50% of patients present with stage III/IV disease: so-called locally advanced head and neck cancer (LAHNC).For LAHNC, the treatment paradigm has shifted from mutilating, ablative surgery towards organ-preserving concomitant cisplatin-based chemoradiotherapy [1].Compared with surgery, chemoradiotherapy delivers equivalent or better locoregional control and disease-free survival with significantly better functional outcomes [1].Nonetheless, 5-year disease-free and overall survival (30-40%) rates are suboptimal [2].Strategies to improve outcomes by escalating conventionally delivered radiotherapy and/or cytotoxic chemotherapy are appealing, but they pose unacceptable risks of severe acute and late normal tissue damage and threaten chronic structural, cosmetic and functional deficits that negatively impact quality of life [3].Recent technical developments in physical targeting of radiation delivery, including intensity-modulated and image-guided therapy, offer a way of safely escalating tumour dose without exceeding normal tissue tolerances.Also, a clearer understanding of the radiation-induced DNA damage response (RIDDR) opens up the possibility of developing tumour-selective biological response modifiers to enhance the effect of radiotherapy/chemoradiotherapy.The potential value of such therapies has been proven by the translation of therapy targeted to the epidermal growth factor receptor (EGFR), cetuximab, from preclinical studies to a positive phase III trial in combination with radiation [4].In addition, smallmolecule tyrosine kinase inhibitors have been tested [5,6].Recently, biological studies have characterised LAHNC as a disease spectrum, divisible into different prognostic groups on the basis of demographic (tobacco exposure), clinical/ radiological (T and N stage) and molecular pathological (human papillomavirus (HPV) status) variables [7].In addition, we are beginning to understand the molecular landscape of LAHNC more clearly [8].As a result, we can escape the standard model whereby all patients receive treatment according to a 'one size suits all' philosophy.Instead, we are moving to-