Azoury SaÏd C, Gilmore Richard C, Shukla Vivek
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21202, USA.
Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Discov Med. 2016 Jun;21(118):507-16.
Squamous cell carcinoma is one of the most frequent tumors of the head and neck and often presents at an advanced-stage. Traditionally, treatment for head and neck squamous cell carcinoma (HNSCC) has included surgery, radiation, and chemotherapy depending on both the site and stage of disease. Although the treatment approach for local disease is often standardized, the management of recurrent and advanced disease is evolving. A better understanding of the molecular mechanisms of HNSCC has led to numerous promising investigations and the push for the development of novel therapies. Similarly, over the past several decades, growing data supports the notion that an individual's immune system can be manipulated in such a way to help eradicate cancer. The success of immunotherapeutic agents such as interleukin therapy and immune checkpoint inhibitor blockade in cancer, particularly advanced-stage melanoma, has stimulated researchers to uncover similar success stories in HNSCC. Examples of immunotherapeutics that are being studied for the treatment of HNSCC include adoptive T-cell therapy, vaccines, and immune checkpoint inhibitor proteins (e.g., anti-CTLA-4, -PD-1, -PD-L1). Molecularly targeted agents of interest include inhibitors of transmembrane growth factor receptors, angiogenesis, and PI3K/AKT/mTOR and NOTCH signaling pathways. To date, cetuximab, an epidermal growth factor receptor inhibitor, is the only targeted agent for HNSCC that was approved by the Federal Food and Drug Administration (FDA) on the basis that it improves overall survival when combined with chemotherapy or radiation. Herein, the authors provide an up-to-date review of immunotherapeutic and molecularly targeted agents for the treatment of HNSCC.
鳞状细胞癌是头颈部最常见的肿瘤之一，且常呈晚期出现。传统上，头颈部鳞状细胞癌（HNSCC）的治疗包括手术、放疗和化疗，具体治疗方式取决于疾病的部位和分期。尽管局部疾病的治疗方法通常是标准化的，但复发性和晚期疾病的管理仍在不断发展。对HNSCC分子机制的更好理解引发了众多有前景的研究，并推动了新型疗法的开发。同样，在过去几十年中，越来越多的数据支持这样一种观点，即个体的免疫系统可以通过某种方式进行调控以帮助根除癌症。免疫治疗药物如白细胞介素疗法和免疫检查点抑制剂在癌症治疗中，尤其是晚期黑色素瘤治疗中的成功，刺激研究人员在HNSCC中寻找类似的成功案例。正在研究用于治疗HNSCC的免疫治疗方法包括过继性T细胞疗法、疫苗和免疫检查点抑制剂蛋白（如抗CTLA-4、-PD-1、-PD-L1）。感兴趣的分子靶向药物包括跨膜生长因子受体抑制剂、血管生成抑制剂以及PI3K/AKT/mTOR和NOTCH信号通路抑制剂。迄今为止，表皮生长因子受体抑制剂西妥昔单抗是唯一一种经美国食品药品监督管理局（FDA）批准的用于HNSCC的靶向药物，其获批依据是与化疗或放疗联合使用时可提高总生存率。在此，作者提供了一篇关于治疗HNSCC的免疫治疗和分子靶向药物的最新综述。
