Approximately 600,000 new cases of head and neck cancer arise worldwide each year. Of these, a large majority are head and neck squamous cell carcinomas (HNSCC). Conventional treatments, including surgical excision followed by radiation and/or chemoradiotherapy have limited efficacy and are associated with substantial toxicity. To date, key targets for molecular targeted therapy in HNSCC are epidermal growth factor receptors and angiogenesis-related factors. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) and it is the only targeted therapy approved by the United States Food and Drug Administration for the treatment of HNSCC. Cetuximab in combination with radiotherapy represents a standard approach for newly diagnosed patients who are unable to tolerate platinum chemotherapy. Despite efficacy in preclinical HNSCC models, cetuximab is only effective in a subset of HNSCC patients, most likely due to the high heterogeneity of this cancer. Additional targets under active investigation include the PI3K/Akt pathway, the Ras-MAPK-ERK pathway and the JAK/STAT pathway, among others. Combining molecular targeted therapies and radiation may allow for deintensification of radiotherapy thereby reducing radiation toxicities and improving treatment outcomes. Here we review the preclinical and clinical data in support of treatment strategies that combined targeted therapy with radiation in HNSCC.

中文翻译：

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分子靶向疗法与放射疗法在头颈癌中的整合。

每年全世界大约有600,000例新的头颈癌病例出现。其中，绝大多数是头颈部鳞状细胞癌（HNSCC）。包括外科切除，放射线和/或放化疗在内的常规治疗方法疗效有限，并伴有明显的毒性。迄今为止，HNSCC中分子靶向治疗的关键靶点是表皮生长因子受体和血管生成相关因子。西妥昔单抗是靶向表皮生长因子受体（EGFR）的单克隆抗体，它是美国食品和药物管理局批准的用于治疗HNSCC的唯一靶向疗法。西妥昔单抗联合放疗是不能耐受铂类化学疗法的新诊断患者的标准方法。尽管在临床前HNSCC模型中有效，但是西妥昔单抗仅在一部分HNSCC患者中有效，这很可能是由于该癌症的高度异质性。积极调查中的其他目标包括PI3K / Akt途径，Ras-MAPK-ERK途径和JAK / STAT途径等。分子靶向疗法和放射疗法的结合可以使放疗的强度降低，从而降低放射毒性并改善治疗效果。在这里，我们回顾了临床前和临床数据，以支持将HNSCC中的靶向治疗与放射治疗相结合的治疗策略。Ras-MAPK-ERK途径和JAK / STAT途径等等。分子靶向疗法和放射疗法的结合可以使放疗的强度降低，从而降低放射毒性并改善治疗效果。在这里，我们回顾了临床前和临床数据，以支持将HNSCC中的靶向治疗与放射治疗相结合的治疗策略。Ras-MAPK-ERK途径和JAK / STAT途径等等。分子靶向疗法和放射疗法的结合可以使放疗的强度降低，从而降低放射毒性并改善治疗效果。在这里，我们回顾了临床前和临床数据，以支持将HNSCC中的靶向治疗与放射治疗相结合的治疗策略。