Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma.
Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma.
复制标题
DOI：
10.1007/s12032-017-0918-1
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Suchorska WM
中科院分区：
文献类型：
--
作者：
Blaszczak W;Barczak W;Wegner A;Golusinski W;Suchorska WM
头颈部鳞状细胞癌（HNSCC）是一组异质性恶性肿瘤，每年影响超过500，000例患者。治疗失败通常是由于这些肿瘤的异质性和与治疗相关的严重不良反应。HNSCC中常见的免疫系统损伤通过介导肿瘤逃逸机制进一步导致治疗失败。迄今为止，唯一临床批准的靶向治疗药物是西妥昔单抗，一种结合并抑制表皮生长因子受体的单克隆抗体（mAb），该受体在HNSCC中广泛过表达。西妥昔单抗已被证明诱导抗体依赖性细胞毒性，进一步放大其治疗效果。HNSCC细胞的DNA测序已经确定了突变基因的存在，从而使其蛋白质产物成为治疗抑制的潜在靶点。已发现免疫机制对致癌作用具有显著影响，从而为支持鉴定具有免疫调节特性的抗癌化合物的努力提供了理论基础。在新的靶向药物的快速发展的背景下，本文的目的是回顾我们目前对HNSCC的认识，并回顾近年来推出的新型抗癌药物（单克隆抗体和TKI），包括评估其疗效和作用机制。
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC. Cetuximab has been proven to induce antibody-dependent cellular cytotoxicity, further magnifying its therapeutic effect. DNA sequencing of HNSCC cells has identified the presence of mutated genes, thus making their protein products potential targets for therapeutic inhibition. Immune mechanisms have been found to have a significant impact on carcinogenesis, thus providing the rationale to support efforts to identify anticancer compounds with immunomodulatory properties. In the context of the rapid development of novel targeted agents, the aim of the present paper is to review our current understanding of HNSCC and to review the novel anticancer agents (mAbs and TKIs) introduced in recent years, including an assessment of their efficacy and mechanisms of action.