Choi S, Myers J N
Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 441, [corrected] Houston, TX 77030-4009, USA.
J Dent Res. 2008 Jan;87(1):14-32. doi: 10.1177/154405910808700104.
The development of oral squamous cell carcinoma (OSCC) is a multistep process requiring the accumulation of multiple genetic alterations, influenced by a patient's genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and viral infection. Tumorigenic genetic alterations consist of two major types: tumor suppressor genes, which promote tumor development when inactivated; and oncogenes, which promote tumor development when activated. Tumor suppressor genes can be inactivated through genetic events such as mutation, loss of heterozygosity, or deletion, or by epigenetic modifications such as DNA methylation or chromatin remodeling. Oncogenes can be activated through overexpression due to gene amplification, increased transcription, or changes in structure due to mutations that lead to increased transforming activity. This review focuses on the molecular mechanisms of oral carcinogenesis and the use of biologic therapy to specifically target molecules altered in OSCC. The rapid progress that has been made in our understanding of the molecular alterations contributing to the development of OSCC is leading to improvements in the early diagnosis of tumors and the refinement of biologic treatments individualized to the specific characteristics of a patient's tumor.
口腔鳞状细胞癌（OSCC）的发生是一个多步骤过程，需要多种基因改变的积累，这受到患者遗传易感性以及环境因素的影响，包括烟草、酒精、慢性炎症和病毒感染。致瘤性基因改变主要包括两种类型：肿瘤抑制基因，其失活时促进肿瘤发展；以及癌基因，其激活时促进肿瘤发展。肿瘤抑制基因可通过诸如突变、杂合性缺失或缺失等遗传事件失活，或通过诸如DNA甲基化或染色质重塑等表观遗传修饰失活。癌基因可通过基因扩增导致的过表达、转录增加或由于导致转化活性增加的突变引起的结构改变而被激活。本综述重点关注口腔癌发生的分子机制以及使用生物疗法特异性靶向OSCC中改变的分子。我们对导致OSCC发生的分子改变的理解取得的快速进展正促使肿瘤早期诊断的改善以及根据患者肿瘤的特定特征定制生物治疗的优化。
