Lippman Scott M, Sudbø Jon, Hong Waun Ki
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
J Clin Oncol. 2005 Jan 10;23(2):346-56. doi: 10.1200/JCO.2005.09.128.
The multifaceted rationale for molecular-targeted prevention of oral cancer is strong. Oral cancer is a major global threat to public health, causing great morbidity and mortality rates that have not improved in decades. Oral cancer development is a tobacco-related multistep and multifocal process involving field carcinogenesis and intraepithelial clonal spread. Biomarkers of genomic instability, such as aneuploidy and allelic imbalance, can accurately measure the cancer risk of oral premalignant lesions, or intraepithelial neoplasia (IEN). Retinoid-oral IEN studies (eg, of retinoic acid receptor-beta, p53, genetic instability, loss of heterozygosity, and cyclin D1) have advanced the overall understanding of the biology of intraepithelial carcinogenesis and of preventive agent molecular mechanisms and targets-important advances for monitoring preventive interventions and assessing cancer risk and pharmacogenomics. Clinical management of oral IEN varies from watchful waiting to complete resection, although complete resection does not prevent oral cancer in high-risk patients. New approaches, such as interventions with molecular-targeted agents and agent combinations in molecularly defined high-risk oral IEN patients, are urgently needed to reduce the devastating worldwide consequences of oral cancer.
分子靶向预防口腔癌具有多方面的充分理由。口腔癌是对全球公共卫生的重大威胁，导致的发病率和死亡率极高，且几十年来一直没有改善。口腔癌的发展是一个与烟草相关的多步骤、多灶性过程，涉及场癌化和上皮内克隆性扩散。基因组不稳定的生物标志物，如非整倍体和等位基因失衡，能够准确测量口腔癌前病变或上皮内瘤变（IEN）的癌症风险。维甲酸 - 口腔IEN研究（例如关于维甲酸受体 - β、p53、基因不稳定、杂合性缺失和细胞周期蛋白D1的研究）推进了对上皮内癌发生生物学以及预防剂分子机制和靶点的全面理解，这些都是监测预防干预措施、评估癌症风险和药物基因组学的重要进展。口腔IEN的临床管理方式多样，从密切观察等待到完全切除，不过对于高危患者，完全切除并不能预防口腔癌。迫切需要新的方法，例如对分子定义的高危口腔IEN患者采用分子靶向药物和药物组合进行干预，以减少口腔癌在全球范围内造成的毁灭性后果。
