Therapeutic Insights from Genomic Studies of Head and NeckSquamous Cell Carcinomas

摘要

Summary: Large and comprehensive genomic surveys of head and neck squamous cell carcinomas (HNSCC) are now greatly increasing our understanding of the diversity of this disease and the key genomic changes that drive these tumors. The results from these studies are beginning to inform the introduction of novel therapies for patients with HNSCCs. Here, we review some of the key findings from recent genomic studies of head and neck cancers, including the most comprehensive study to date from The Cancer Genome Atlas Network. INTRODUCTION Head and neck squamous cell carcinomas (HNSCC) are the fifth most common malignancy worldwide and comprise a diverse set of cancers arising in the upper aerodigestive tract mucosa (1). Unlike many other epithelial cancers, the majority of HNSCCs present at a locally advanced stage with cervical lymph node metastases. More than 90% of patients are treated with curative intent using a combination of surgery, radiotherapy, and chemotherapy (2). To date, treatment approaches have been dictated by the anatomic site of the primary tumor, with oral cavity cancers treated primarily with surgical resection and pharyngeal and laryngeal tumors with chemoradiation (3). Although over one half of patients are cured with initial therapy, these treatments are highly morbid, and therapeutic options for individuals who relapse following initial treatment are limited (4). In the absence of information regarding the biologic underpinnings of individual tumors, predictive biomarkers have been lacking to guide therapy in both the initial treatment setting and in the treatment of relapsed/refractory disease. Establishing robust therapeutic biomarkers in HNSCCs has been challenging for several reasons, including the heterogeneity of these tumors that display diversity in terms of their anatomy, clinical characteristics, and in their association with conventional risk factors, such as tobacco and alcohol exposure, as well as with infection with the oncogenic human papillomavirus (HPV) and Epstein-Barr Virus (EBV; refs. 2, 5).